<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:01a081e7-202e-738c-8325-9bb0a90694a9,g:6850ddf0-b39c-4440-a899-9c542bb5afd1-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSSUnaudited" xlink:type="simple" xlink:href="pacb-20260930.xsd#CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSSUnaudited"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSSUnaudited" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_01a081e7-21c9-713b-ae73-8c1f7d794529" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_StatementTable_01a081e7-21c9-713b-ae73-8c1f7d794529" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a081e7-21c9-7070-b617-e07c40d60d8e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_01a081e7-21c9-713b-ae73-8c1f7d794529" xlink:to="loc_srt_ProductOrServiceAxis_01a081e7-21c9-7070-b617-e07c40d60d8e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21c9-7070-b617-e07c40d60d8e_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21c9-7070-b617-e07c40d60d8e" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21c9-7070-b617-e07c40d60d8e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21c9-7685-8cfa-3d163bab377a" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21c9-7070-b617-e07c40d60d8e" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21c9-7685-8cfa-3d163bab377a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_01a081e7-21c9-787b-ac1e-a18cf0b983cb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a081e7-21c9-7685-8cfa-3d163bab377a" xlink:to="loc_us-gaap_ProductMember_01a081e7-21c9-787b-ac1e-a18cf0b983cb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ServiceAndOtherMember_01a081e7-21c9-7748-a90b-c6e11de52031" xlink:href="pacb-20260930.xsd#pacb_ServiceAndOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a081e7-21c9-7685-8cfa-3d163bab377a" xlink:to="loc_pacb_ServiceAndOtherMember_01a081e7-21c9-7748-a90b-c6e11de52031" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_01a081e7-21c9-7e5b-9d81-73fc02a03f0d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenuesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_RevenuesAbstract_01a081e7-21c9-7e5b-9d81-73fc02a03f0d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_01a081e7-21c9-729d-8ab8-ed795df5f830" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_01a081e7-21c9-7e5b-9d81-73fc02a03f0d" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_01a081e7-21c9-729d-8ab8-ed795df5f830" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfRevenueAbstract_01a081e7-21c9-77b4-99a7-7de9b153844a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostOfRevenueAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_CostOfRevenueAbstract_01a081e7-21c9-77b4-99a7-7de9b153844a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServiceExcludingDepreciationDepletionAndAmortization_01a081e7-21c9-7610-a315-d314eb0477b4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostOfGoodsAndServiceExcludingDepreciationDepletionAndAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostOfRevenueAbstract_01a081e7-21c9-77b4-99a7-7de9b153844a" xlink:to="loc_us-gaap_CostOfGoodsAndServiceExcludingDepreciationDepletionAndAmortization_01a081e7-21c9-7610-a315-d314eb0477b4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSoldAmortization_01a081e7-21c9-75e0-b665-df77c65a324d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostOfGoodsAndServicesSoldAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostOfRevenueAbstract_01a081e7-21c9-77b4-99a7-7de9b153844a" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSoldAmortization_01a081e7-21c9-75e0-b665-df77c65a324d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LossOnPurchaseCommitment_01a081e7-21c9-7aaf-ad6a-cdf0ed87088e" xlink:href="pacb-20260930.xsd#pacb_LossOnPurchaseCommitment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostOfRevenueAbstract_01a081e7-21c9-77b4-99a7-7de9b153844a" xlink:to="loc_pacb_LossOnPurchaseCommitment_01a081e7-21c9-7aaf-ad6a-cdf0ed87088e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfRevenue_01a081e7-21c9-7863-ba95-87e60d18ebf9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostOfRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostOfRevenueAbstract_01a081e7-21c9-77b4-99a7-7de9b153844a" xlink:to="loc_us-gaap_CostOfRevenue_01a081e7-21c9-7863-ba95-87e60d18ebf9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GrossProfit_01a081e7-21c9-77b9-ab78-778bf0466854" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GrossProfit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_GrossProfit_01a081e7-21c9-77b9-ab78-778bf0466854" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpensesAbstract_01a081e7-21c9-7bc6-bdad-f532428a0203" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_OperatingExpensesAbstract_01a081e7-21c9-7bc6-bdad-f532428a0203" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_01a081e7-21c9-738b-a3cd-71955faacdc8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_01a081e7-21c9-7bc6-bdad-f532428a0203" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_01a081e7-21c9-738b-a3cd-71955faacdc8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_01a081e7-21c9-7880-9440-d5db3026b062" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_01a081e7-21c9-7bc6-bdad-f532428a0203" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_01a081e7-21c9-7880-9440-d5db3026b062" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21c9-751e-bf2a-54103a4e6367" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillAndIntangibleAssetImpairment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_01a081e7-21c9-7bc6-bdad-f532428a0203" xlink:to="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21c9-751e-bf2a-54103a4e6367" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SettlementCharges_01a081e7-21c9-70f0-9b42-f28856a5714a" xlink:href="pacb-20260930.xsd#pacb_SettlementCharges"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_01a081e7-21c9-7bc6-bdad-f532428a0203" xlink:to="loc_pacb_SettlementCharges_01a081e7-21c9-70f0-9b42-f28856a5714a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnDispositionOfAssets1_01a081e7-21c9-7f0d-b55d-c4dca04ea0d0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GainLossOnDispositionOfAssets1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_01a081e7-21c9-7bc6-bdad-f532428a0203" xlink:to="loc_us-gaap_GainLossOnDispositionOfAssets1_01a081e7-21c9-7f0d-b55d-c4dca04ea0d0" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_AmortizationOfAcquiredIntangibleAssets_01a081e7-21c9-744c-9655-4a5794774d82" xlink:href="pacb-20260930.xsd#pacb_AmortizationOfAcquiredIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_01a081e7-21c9-7bc6-bdad-f532428a0203" xlink:to="loc_pacb_AmortizationOfAcquiredIntangibleAssets_01a081e7-21c9-744c-9655-4a5794774d82" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_01a081e7-21c9-7aba-b75a-f3589f8cb0a6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_01a081e7-21c9-7bc6-bdad-f532428a0203" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_01a081e7-21c9-7aba-b75a-f3589f8cb0a6" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_01a081e7-21c9-7d06-beb1-a8a202c3ddb8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_01a081e7-21c9-7bc6-bdad-f532428a0203" xlink:to="loc_us-gaap_OperatingExpenses_01a081e7-21c9-7d06-beb1-a8a202c3ddb8" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_01a081e7-21c9-764b-a276-087e9309a81b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_OperatingIncomeLoss_01a081e7-21c9-764b-a276-087e9309a81b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_01a081e7-21c9-79e3-97fc-f04f73a2603d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_InterestExpenseNonoperating_01a081e7-21c9-79e3-97fc-f04f73a2603d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_01a081e7-21c9-7056-a9db-4be2dcaf66fc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_01a081e7-21c9-7056-a9db-4be2dcaf66fc" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_01a081e7-21c9-72e3-bc78-102bbe4d2266" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_01a081e7-21c9-72e3-bc78-102bbe4d2266" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_01a081e7-21c9-7737-b4b0-e8506e1ad712" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_01a081e7-21c9-7737-b4b0-e8506e1ad712" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_01a081e7-21c9-7c15-b0d1-355ca2b63b68" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_NetIncomeLoss_01a081e7-21c9-7c15-b0d1-355ca2b63b68" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_01a081e7-21c9-7a28-b791-aff9deb9f0fb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_01a081e7-21c9-7a28-b791-aff9deb9f0fb" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_01a081e7-21c9-786e-9407-036360f71852" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_01a081e7-21c9-7a28-b791-aff9deb9f0fb" xlink:to="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_01a081e7-21c9-786e-9407-036360f71852" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_01a081e7-21c9-7558-b248-15fb2429a57e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_ComprehensiveIncomeNetOfTax_01a081e7-21c9-7558-b248-15fb2429a57e" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IncomeLossPerShareAbstract_01a081e7-21c9-7fc4-96d7-4e8d726d5d53" xlink:href="pacb-20260930.xsd#pacb_IncomeLossPerShareAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_pacb_IncomeLossPerShareAbstract_01a081e7-21c9-7fc4-96d7-4e8d726d5d53" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_01a081e7-21c9-7cfb-a585-87855965649f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_IncomeLossPerShareAbstract_01a081e7-21c9-7fc4-96d7-4e8d726d5d53" xlink:to="loc_us-gaap_EarningsPerShareBasic_01a081e7-21c9-7cfb-a585-87855965649f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_01a081e7-21c9-78c2-ba07-49e7f3e8a56c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_IncomeLossPerShareAbstract_01a081e7-21c9-7fc4-96d7-4e8d726d5d53" xlink:to="loc_us-gaap_EarningsPerShareDiluted_01a081e7-21c9-78c2-ba07-49e7f3e8a56c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasicOtherDisclosuresAbstract_01a081e7-21c9-7cf7-b20d-d3be27c79802" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EarningsPerShareBasicOtherDisclosuresAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21c9-7a08-a992-1be489a8bbad" xlink:to="loc_us-gaap_EarningsPerShareBasicOtherDisclosuresAbstract_01a081e7-21c9-7cf7-b20d-d3be27c79802" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_01a081e7-21c9-7741-9e3c-7261f46a6aa8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicOtherDisclosuresAbstract_01a081e7-21c9-7cf7-b20d-d3be27c79802" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_01a081e7-21c9-7741-9e3c-7261f46a6aa8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_01a081e7-21c9-7a9f-abc7-dd78c48d982e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareBasicOtherDisclosuresAbstract_01a081e7-21c9-7cf7-b20d-d3be27c79802" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_01a081e7-21c9-7a9f-abc7-dd78c48d982e" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITYDEFICITUnaudited" xlink:type="simple" xlink:href="pacb-20260930.xsd#CONDENSEDCONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITYDEFICITUnaudited"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITYDEFICITUnaudited" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_01a081e7-21ca-7bc2-998c-e943e7631be2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_01a081e7-21ca-7b81-9e53-b4797d417dd8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21ca-7bc2-998c-e943e7631be2" xlink:to="loc_us-gaap_StatementTable_01a081e7-21ca-7b81-9e53-b4797d417dd8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_01a081e7-21ca-7559-98b4-5530c2f1ed65" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_01a081e7-21ca-7b81-9e53-b4797d417dd8" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_01a081e7-21ca-7559-98b4-5530c2f1ed65" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_01a081e7-21ca-7559-98b4-5530c2f1ed65_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_01a081e7-21ca-7559-98b4-5530c2f1ed65" xlink:to="loc_us-gaap_EquityComponentDomain_01a081e7-21ca-7559-98b4-5530c2f1ed65_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_01a081e7-21ca-7d2a-a17c-cba45d2e9c17" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_01a081e7-21ca-7559-98b4-5530c2f1ed65" xlink:to="loc_us-gaap_EquityComponentDomain_01a081e7-21ca-7d2a-a17c-cba45d2e9c17" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_01a081e7-21ca-7987-9d02-1df916207714" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_01a081e7-21ca-7d2a-a17c-cba45d2e9c17" xlink:to="loc_us-gaap_CommonStockMember_01a081e7-21ca-7987-9d02-1df916207714" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_01a081e7-21ca-72a9-a43d-fe368c23be06" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_01a081e7-21ca-7d2a-a17c-cba45d2e9c17" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_01a081e7-21ca-72a9-a43d-fe368c23be06" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_01a081e7-21ca-70e9-8f12-d8a2067a4517" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_01a081e7-21ca-7d2a-a17c-cba45d2e9c17" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_01a081e7-21ca-70e9-8f12-d8a2067a4517" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_01a081e7-21ca-709b-97fd-aad073a8ea99" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_01a081e7-21ca-7d2a-a17c-cba45d2e9c17" xlink:to="loc_us-gaap_RetainedEarningsMember_01a081e7-21ca-709b-97fd-aad073a8ea99" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a081e7-21ca-7153-aa8c-f32153caf94d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a081e7-21ca-7bc2-998c-e943e7631be2" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a081e7-21ca-7153-aa8c-f32153caf94d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_01a081e7-21ca-7d26-bcb5-83d65f6af60c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a081e7-21ca-7153-aa8c-f32153caf94d" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_01a081e7-21ca-7d26-bcb5-83d65f6af60c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_01a081e7-21ca-76e6-8702-9df846a43c5f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a081e7-21ca-7153-aa8c-f32153caf94d" xlink:to="loc_us-gaap_StockholdersEquity_01a081e7-21ca-76e6-8702-9df846a43c5f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_01a081e7-21ca-79df-8791-3860a3b7a154" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a081e7-21ca-7153-aa8c-f32153caf94d" xlink:to="loc_us-gaap_NetIncomeLoss_01a081e7-21ca-79df-8791-3860a3b7a154" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_01a081e7-21ca-7d56-bed6-302cd8f26226" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a081e7-21ca-7153-aa8c-f32153caf94d" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_01a081e7-21ca-7d56-bed6-302cd8f26226" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_01a081e7-21ca-7e79-ac5a-2a6b2df0501d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a081e7-21ca-7153-aa8c-f32153caf94d" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_01a081e7-21ca-7e79-ac5a-2a6b2df0501d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_01a081e7-21ca-7412-a0c7-4d0c6361a95f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a081e7-21ca-7153-aa8c-f32153caf94d" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_01a081e7-21ca-7412-a0c7-4d0c6361a95f" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_01a081e7-21ca-7826-b8f0-2ae61dfcef98" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a081e7-21ca-7153-aa8c-f32153caf94d" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_01a081e7-21ca-7826-b8f0-2ae61dfcef98" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_01a081e7-21ca-7b84-8139-d40a651744bc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_01a081e7-21ca-7cc9-9cd8-a697e43a5a04" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/ORGANIZATIONANDSIGNIFICANTACCOUNTINGPOLICIESDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#ORGANIZATIONANDSIGNIFICANTACCOUNTINGPOLICIESDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/ORGANIZATIONANDSIGNIFICANTACCOUNTINGPOLICIESDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SummaryOfSignificantAccountingPoliciesLineItems_01a081e7-21ca-75eb-859d-119b490c72cf" xlink:href="pacb-20260930.xsd#pacb_SummaryOfSignificantAccountingPoliciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SummaryOfSignificantAccountingPoliciesTable_01a081e7-21ca-7bb1-a492-2385c9244100" xlink:href="pacb-20260930.xsd#pacb_SummaryOfSignificantAccountingPoliciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_pacb_SummaryOfSignificantAccountingPoliciesLineItems_01a081e7-21ca-75eb-859d-119b490c72cf" xlink:to="loc_pacb_SummaryOfSignificantAccountingPoliciesTable_01a081e7-21ca-7bb1-a492-2385c9244100" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_01a081e7-21ca-7aa3-bf35-be771cd2f75c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_SummaryOfSignificantAccountingPoliciesTable_01a081e7-21ca-7bb1-a492-2385c9244100" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_01a081e7-21ca-7aa3-bf35-be771cd2f75c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_01a081e7-21ca-7aa3-bf35-be771cd2f75c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_01a081e7-21ca-7aa3-bf35-be771cd2f75c" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_01a081e7-21ca-7aa3-bf35-be771cd2f75c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_01a081e7-21ca-74f0-a1c9-7b9cf97e5d92" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_01a081e7-21ca-7aa3-bf35-be771cd2f75c" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_01a081e7-21ca-74f0-a1c9-7b9cf97e5d92" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableMember_01a081e7-21ca-74f8-8001-4f3a0354d7ae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccountsReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_01a081e7-21ca-74f0-a1c9-7b9cf97e5d92" xlink:to="loc_us-gaap_AccountsReceivableMember_01a081e7-21ca-74f8-8001-4f3a0354d7ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_01a081e7-21ca-7822-accf-f07db1ec57d5" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_SummaryOfSignificantAccountingPoliciesTable_01a081e7-21ca-7bb1-a492-2385c9244100" xlink:to="loc_srt_MajorCustomersAxis_01a081e7-21ca-7822-accf-f07db1ec57d5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_01a081e7-21ca-7822-accf-f07db1ec57d5_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_01a081e7-21ca-7822-accf-f07db1ec57d5" xlink:to="loc_srt_NameOfMajorCustomerDomain_01a081e7-21ca-7822-accf-f07db1ec57d5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_01a081e7-21ca-7c62-aecf-49615a3c0d4b" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_01a081e7-21ca-7822-accf-f07db1ec57d5" xlink:to="loc_srt_NameOfMajorCustomerDomain_01a081e7-21ca-7c62-aecf-49615a3c0d4b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DomesticCustomersMember_01a081e7-21ca-747d-bc11-5fd1782af488" xlink:href="pacb-20260930.xsd#pacb_DomesticCustomersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_01a081e7-21ca-7c62-aecf-49615a3c0d4b" xlink:to="loc_pacb_DomesticCustomersMember_01a081e7-21ca-747d-bc11-5fd1782af488" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_01a081e7-21ca-76db-beef-d431ec94d1c8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_SummaryOfSignificantAccountingPoliciesTable_01a081e7-21ca-7bb1-a492-2385c9244100" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_01a081e7-21ca-76db-beef-d431ec94d1c8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_01a081e7-21ca-76db-beef-d431ec94d1c8_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_01a081e7-21ca-76db-beef-d431ec94d1c8" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_01a081e7-21ca-76db-beef-d431ec94d1c8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_01a081e7-21ca-7dee-9ef9-9cbbad3c7661" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_01a081e7-21ca-76db-beef-d431ec94d1c8" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_01a081e7-21ca-7dee-9ef9-9cbbad3c7661" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_01a081e7-21ca-7da5-b291-0f46dd89698f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CustomerConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_01a081e7-21ca-7dee-9ef9-9cbbad3c7661" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_01a081e7-21ca-7da5-b291-0f46dd89698f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_01a081e7-21ca-7a0b-9af9-23d673b7058b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_SummaryOfSignificantAccountingPoliciesLineItems_01a081e7-21ca-75eb-859d-119b490c72cf" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_01a081e7-21ca-7a0b-9af9-23d673b7058b" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/FINANCIALINSTRUMENTSScheduleofAssetsMeasuredatFairValueonaRecurringBasisDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#FINANCIALINSTRUMENTSScheduleofAssetsMeasuredatFairValueonaRecurringBasisDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/FINANCIALINSTRUMENTSScheduleofAssetsMeasuredatFairValueonaRecurringBasisDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a081e7-21ca-7809-9310-97a2c91ed84c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a081e7-21ca-78aa-a6ec-a922661a5734" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a081e7-21ca-7809-9310-97a2c91ed84c" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a081e7-21ca-78aa-a6ec-a922661a5734" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a081e7-21ca-702f-909d-904e4ba8640d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a081e7-21ca-78aa-a6ec-a922661a5734" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a081e7-21ca-702f-909d-904e4ba8640d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a081e7-21ca-702f-909d-904e4ba8640d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a081e7-21ca-702f-909d-904e4ba8640d" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a081e7-21ca-702f-909d-904e4ba8640d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a081e7-21ca-7f1d-9c38-35d08b65db30" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a081e7-21ca-702f-909d-904e4ba8640d" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a081e7-21ca-7f1d-9c38-35d08b65db30" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_01a081e7-21ca-732e-b9cd-9788ce144867" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a081e7-21ca-7f1d-9c38-35d08b65db30" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_01a081e7-21ca-732e-b9cd-9788ce144867" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_01a081e7-21ca-747e-8c61-d11ea92b9d9f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a081e7-21ca-7f1d-9c38-35d08b65db30" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_01a081e7-21ca-747e-8c61-d11ea92b9d9f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_01a081e7-21ca-7011-a489-38ecee629110" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a081e7-21ca-7f1d-9c38-35d08b65db30" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_01a081e7-21ca-7011-a489-38ecee629110" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByAssetClassAxis_01a081e7-21ca-73db-ba3b-df23963d3c43" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a081e7-21ca-78aa-a6ec-a922661a5734" xlink:to="loc_us-gaap_FairValueByAssetClassAxis_01a081e7-21ca-73db-ba3b-df23963d3c43" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_01a081e7-21ca-73db-ba3b-df23963d3c43_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_01a081e7-21ca-73db-ba3b-df23963d3c43" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_01a081e7-21ca-73db-ba3b-df23963d3c43_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_01a081e7-21ca-7233-a1e9-4b15fea62aeb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_01a081e7-21ca-73db-ba3b-df23963d3c43" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_01a081e7-21ca-7233-a1e9-4b15fea62aeb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsMember_01a081e7-21ca-71c9-8fd2-777ff7dc7cc3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InvestmentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_01a081e7-21ca-7233-a1e9-4b15fea62aeb" xlink:to="loc_us-gaap_InvestmentsMember_01a081e7-21ca-71c9-8fd2-777ff7dc7cc3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_01a081e7-21ca-7e4b-9075-8f9da9e3763e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentsMember_01a081e7-21ca-71c9-8fd2-777ff7dc7cc3" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_01a081e7-21ca-7e4b-9075-8f9da9e3763e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember_01a081e7-21ca-70f1-a017-168dd4200fd1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentsMember_01a081e7-21ca-71c9-8fd2-777ff7dc7cc3" xlink:to="loc_us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember_01a081e7-21ca-70f1-a017-168dd4200fd1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_01a081e7-21ca-7c4c-9c52-86eb1e475a28" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a081e7-21ca-78aa-a6ec-a922661a5734" xlink:to="loc_us-gaap_FinancialInstrumentAxis_01a081e7-21ca-7c4c-9c52-86eb1e475a28" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-7c4c-9c52-86eb1e475a28_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_01a081e7-21ca-7c4c-9c52-86eb1e475a28" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-7c4c-9c52-86eb1e475a28_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-75da-9f25-06784393f31d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_01a081e7-21ca-7c4c-9c52-86eb1e475a28" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-75da-9f25-06784393f31d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsMember_01a081e7-21ca-7538-a4d2-a8a33010fb36" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InvestmentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-75da-9f25-06784393f31d" xlink:to="loc_us-gaap_InvestmentsMember_01a081e7-21ca-7538-a4d2-a8a33010fb36" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsAbstract_01a081e7-21ca-700a-b4b9-b0f07120b833" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a081e7-21ca-7809-9310-97a2c91ed84c" xlink:to="loc_us-gaap_AssetsAbstract_01a081e7-21ca-700a-b4b9-b0f07120b833" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_01a081e7-21ca-72f7-8390-780ae53b99d1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_01a081e7-21ca-700a-b4b9-b0f07120b833" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_01a081e7-21ca-72f7-8390-780ae53b99d1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsFairValueDisclosure_01a081e7-21ca-755e-8cae-7f48bf381c48" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InvestmentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_01a081e7-21ca-700a-b4b9-b0f07120b833" xlink:to="loc_us-gaap_InvestmentsFairValueDisclosure_01a081e7-21ca-755e-8cae-7f48bf381c48" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ShortTermRestrictedCashFairValueDisclosure_01a081e7-21ca-7698-a0b1-7cbf98e47888" xlink:href="pacb-20260930.xsd#pacb_ShortTermRestrictedCashFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_01a081e7-21ca-700a-b4b9-b0f07120b833" xlink:to="loc_pacb_ShortTermRestrictedCashFairValueDisclosure_01a081e7-21ca-7698-a0b1-7cbf98e47888" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LongTermRestrictedCashFairValueDisclosure_01a081e7-21ca-7ada-bcaa-4f6d0fac8164" xlink:href="pacb-20260930.xsd#pacb_LongTermRestrictedCashFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_01a081e7-21ca-700a-b4b9-b0f07120b833" xlink:to="loc_pacb_LongTermRestrictedCashFairValueDisclosure_01a081e7-21ca-7ada-bcaa-4f6d0fac8164" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_01a081e7-21ca-71d5-8de7-5ac6cd17ac4c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_01a081e7-21ca-700a-b4b9-b0f07120b833" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_01a081e7-21ca-71d5-8de7-5ac6cd17ac4c" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/FINANCIALINSTRUMENTSContingentConsiderationDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#FINANCIALINSTRUMENTSContingentConsiderationDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/FINANCIALINSTRUMENTSContingentConsiderationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_01a081e7-21ca-7a6d-9951-5798be66f415" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a081e7-21ca-7b6f-9e05-31a987c66a8d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a081e7-21ca-7a6d-9951-5798be66f415" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a081e7-21ca-7b6f-9e05-31a987c66a8d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7346-bd0d-90b7b744033f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a081e7-21ca-7b6f-9e05-31a987c66a8d" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7346-bd0d-90b7b744033f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7346-bd0d-90b7b744033f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7346-bd0d-90b7b744033f" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7346-bd0d-90b7b744033f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7ab3-9aee-5807d70984c8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7346-bd0d-90b7b744033f" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7ab3-9aee-5807d70984c8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_AptonMember_01a081e7-21ca-737e-840c-2f660e7c9684" xlink:href="pacb-20260930.xsd#pacb_AptonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7ab3-9aee-5807d70984c8" xlink:to="loc_pacb_AptonMember_01a081e7-21ca-737e-840c-2f660e7c9684" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationByTypeAxis_01a081e7-21ca-7066-ab88-b0633afc38c7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContingentConsiderationByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a081e7-21ca-7b6f-9e05-31a987c66a8d" xlink:to="loc_us-gaap_ContingentConsiderationByTypeAxis_01a081e7-21ca-7066-ab88-b0633afc38c7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationTypeDomain_01a081e7-21ca-7066-ab88-b0633afc38c7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContingentConsiderationTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ContingentConsiderationByTypeAxis_01a081e7-21ca-7066-ab88-b0633afc38c7" xlink:to="loc_us-gaap_ContingentConsiderationTypeDomain_01a081e7-21ca-7066-ab88-b0633afc38c7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationTypeDomain_01a081e7-21ca-7836-b0bc-39fc28da79ec" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContingentConsiderationTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ContingentConsiderationByTypeAxis_01a081e7-21ca-7066-ab88-b0633afc38c7" xlink:to="loc_us-gaap_ContingentConsiderationTypeDomain_01a081e7-21ca-7836-b0bc-39fc28da79ec" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_AchievementOfMilestoneMember_01a081e7-21ca-7c42-83d7-c9bfc7edf430" xlink:href="pacb-20260930.xsd#pacb_AchievementOfMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ContingentConsiderationTypeDomain_01a081e7-21ca-7836-b0bc-39fc28da79ec" xlink:to="loc_pacb_AchievementOfMilestoneMember_01a081e7-21ca-7c42-83d7-c9bfc7edf430" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_01a081e7-21ca-70fc-863a-a4045a407664" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a081e7-21ca-7b6f-9e05-31a987c66a8d" xlink:to="loc_srt_CounterpartyNameAxis_01a081e7-21ca-70fc-863a-a4045a407664" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a081e7-21ca-70fc-863a-a4045a407664_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_01a081e7-21ca-70fc-863a-a4045a407664" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a081e7-21ca-70fc-863a-a4045a407664_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a081e7-21ca-7d10-8e0a-06d54d2e27c4" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_01a081e7-21ca-70fc-863a-a4045a407664" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a081e7-21ca-7d10-8e0a-06d54d2e27c4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IlluminaCambridgeLimitedMember_01a081e7-21ca-7b0f-a22b-5b3c7f11a4d4" xlink:href="pacb-20260930.xsd#pacb_IlluminaCambridgeLimitedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a081e7-21ca-7d10-8e0a-06d54d2e27c4" xlink:to="loc_pacb_IlluminaCambridgeLimitedMember_01a081e7-21ca-7b0f-a22b-5b3c7f11a4d4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisposalGroupClassificationAxis_01a081e7-21ca-72a4-84ca-8927251f0f92" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisposalGroupClassificationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a081e7-21ca-7b6f-9e05-31a987c66a8d" xlink:to="loc_us-gaap_DisposalGroupClassificationAxis_01a081e7-21ca-72a4-84ca-8927251f0f92" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisposalGroupClassificationDomain_01a081e7-21ca-72a4-84ca-8927251f0f92_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisposalGroupClassificationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DisposalGroupClassificationAxis_01a081e7-21ca-72a4-84ca-8927251f0f92" xlink:to="loc_us-gaap_DisposalGroupClassificationDomain_01a081e7-21ca-72a4-84ca-8927251f0f92_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisposalGroupClassificationDomain_01a081e7-21ca-7bd2-9f51-ed4bb2b99ff8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisposalGroupClassificationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DisposalGroupClassificationAxis_01a081e7-21ca-72a4-84ca-8927251f0f92" xlink:to="loc_us-gaap_DisposalGroupClassificationDomain_01a081e7-21ca-7bd2-9f51-ed4bb2b99ff8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisposalGroupNotDiscontinuedOperationsMember_01a081e7-21ca-7e95-a72b-621fc235f779" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisposalGroupNotDiscontinuedOperationsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisposalGroupClassificationDomain_01a081e7-21ca-7bd2-9f51-ed4bb2b99ff8" xlink:to="loc_us-gaap_DisposalGroupNotDiscontinuedOperationsMember_01a081e7-21ca-7e95-a72b-621fc235f779" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a081e7-21ca-78c8-8750-c7a185ad13c2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a081e7-21ca-7a6d-9951-5798be66f415" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a081e7-21ca-78c8-8750-c7a185ad13c2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_BusinessCombinationConsiderationTransferredRevenueAchievementMilestone_01a081e7-21ca-76ce-8986-fcf6d8f1086a" xlink:href="pacb-20260930.xsd#pacb_BusinessCombinationConsiderationTransferredRevenueAchievementMilestone"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a081e7-21ca-7a6d-9951-5798be66f415" xlink:to="loc_pacb_BusinessCombinationConsiderationTransferredRevenueAchievementMilestone_01a081e7-21ca-76ce-8986-fcf6d8f1086a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_BusinessCombinationContingentConsiderationLiabilityMeasurementPeriod_01a081e7-21ca-7321-8058-453b7197e5cd" xlink:href="pacb-20260930.xsd#pacb_BusinessCombinationContingentConsiderationLiabilityMeasurementPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a081e7-21ca-7a6d-9951-5798be66f415" xlink:to="loc_pacb_BusinessCombinationContingentConsiderationLiabilityMeasurementPeriod_01a081e7-21ca-7321-8058-453b7197e5cd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisposalGroupIncludingDiscontinuedOperationConsideration_01a081e7-21ca-7128-928a-547c584246c6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisposalGroupIncludingDiscontinuedOperationConsideration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a081e7-21ca-7a6d-9951-5798be66f415" xlink:to="loc_us-gaap_DisposalGroupIncludingDiscontinuedOperationConsideration_01a081e7-21ca-7128-928a-547c584246c6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_AssetPurchaseAgreementCovenantNetCashProceedsPaidPercentage_01a081e7-21ca-7799-a55d-80245e93d962" xlink:href="pacb-20260930.xsd#pacb_AssetPurchaseAgreementCovenantNetCashProceedsPaidPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a081e7-21ca-7a6d-9951-5798be66f415" xlink:to="loc_pacb_AssetPurchaseAgreementCovenantNetCashProceedsPaidPercentage_01a081e7-21ca-7799-a55d-80245e93d962" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleOfProductiveAssets_01a081e7-21ca-7d84-a69d-b3eac446fcfb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromSaleOfProductiveAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a081e7-21ca-7a6d-9951-5798be66f415" xlink:to="loc_us-gaap_ProceedsFromSaleOfProductiveAssets_01a081e7-21ca-7d84-a69d-b3eac446fcfb" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DisposalGroupTransactionCosts_01a081e7-21ca-7c90-b515-5aaf0d03c2bf" xlink:href="pacb-20260930.xsd#pacb_DisposalGroupTransactionCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a081e7-21ca-7a6d-9951-5798be66f415" xlink:to="loc_pacb_DisposalGroupTransactionCosts_01a081e7-21ca-7c90-b515-5aaf0d03c2bf" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_01a081e7-21ca-7c72-a929-735e9dc45b1f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a081e7-21ca-7a6d-9951-5798be66f415" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_01a081e7-21ca-7c72-a929-735e9dc45b1f" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/FINANCIALINSTRUMENTSScheduleofCashCashEquivalentsRestrictedCashandInvestmentsDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#FINANCIALINSTRUMENTSScheduleofCashCashEquivalentsRestrictedCashandInvestmentsDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/FINANCIALINSTRUMENTSScheduleofCashCashEquivalentsRestrictedCashandInvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a081e7-21ca-7478-99cf-9a225d6705c7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_01a081e7-21ca-76d0-a5cb-fb6e456d0324" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a081e7-21ca-7478-99cf-9a225d6705c7" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_01a081e7-21ca-76d0-a5cb-fb6e456d0324" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_01a081e7-21ca-74ca-9bb6-fcb79ff7cff7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_01a081e7-21ca-76d0-a5cb-fb6e456d0324" xlink:to="loc_us-gaap_FinancialInstrumentAxis_01a081e7-21ca-74ca-9bb6-fcb79ff7cff7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-74ca-9bb6-fcb79ff7cff7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_01a081e7-21ca-74ca-9bb6-fcb79ff7cff7" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-74ca-9bb6-fcb79ff7cff7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-713b-817a-3d340295868a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_01a081e7-21ca-74ca-9bb6-fcb79ff7cff7" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-713b-817a-3d340295868a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsMember_01a081e7-21ca-71fb-88a4-39c07516e0d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-713b-817a-3d340295868a" xlink:to="loc_us-gaap_CashAndCashEquivalentsMember_01a081e7-21ca-71fb-88a4-39c07516e0d7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsMember_01a081e7-21ca-7d82-bb3e-db3551b5a5e5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InvestmentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a081e7-21ca-713b-817a-3d340295868a" xlink:to="loc_us-gaap_InvestmentsMember_01a081e7-21ca-7d82-bb3e-db3551b5a5e5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_01a081e7-21ca-7180-beb6-40b101bede64" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentsMember_01a081e7-21ca-7d82-bb3e-db3551b5a5e5" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_01a081e7-21ca-7180-beb6-40b101bede64" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember_01a081e7-21ca-7a76-956a-71aff3ecb690" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_InvestmentsMember_01a081e7-21ca-7d82-bb3e-db3551b5a5e5" xlink:to="loc_us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember_01a081e7-21ca-7a76-956a-71aff3ecb690" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestAfterAllowanceForCreditLoss_01a081e7-21ca-74cf-9a44-f52b9e89de57" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestAfterAllowanceForCreditLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a081e7-21ca-7478-99cf-9a225d6705c7" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestAfterAllowanceForCreditLoss_01a081e7-21ca-74cf-9a44-f52b9e89de57" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_01a081e7-21ca-709d-aefc-f55d54486dd1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a081e7-21ca-7478-99cf-9a225d6705c7" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_01a081e7-21ca-709d-aefc-f55d54486dd1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_01a081e7-21ca-754e-8a83-bb688780e4ab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a081e7-21ca-7478-99cf-9a225d6705c7" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_01a081e7-21ca-754e-8a83-bb688780e4ab" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest_01a081e7-21ca-7c81-a5b4-49c76fa5edbf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a081e7-21ca-7478-99cf-9a225d6705c7" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest_01a081e7-21ca-7c81-a5b4-49c76fa5edbf" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashCurrent_01a081e7-21ca-7298-8053-51d7fed2a9b2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a081e7-21ca-7478-99cf-9a225d6705c7" xlink:to="loc_us-gaap_RestrictedCashCurrent_01a081e7-21ca-7298-8053-51d7fed2a9b2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsNoncurrent_01a081e7-21ca-773e-ad34-4cd285987453" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashAndCashEquivalentsNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a081e7-21ca-7478-99cf-9a225d6705c7" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsNoncurrent_01a081e7-21ca-773e-ad34-4cd285987453" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/BALANCESHEETCOMPONENTSNarrativeDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#BALANCESHEETCOMPONENTSNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/BALANCESHEETCOMPONENTSNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:href="pacb-20260930.xsd#pacb_ScheduleOfBalanceSheetComponentsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:href="pacb-20260930.xsd#pacb_ScheduleOfBalanceSheetComponentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7b66-a33c-ba05b55f365c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7b66-a33c-ba05b55f365c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_AptonMember_01a081e7-21ca-7314-8e22-afcfe6192ce1" xlink:href="pacb-20260930.xsd#pacb_AptonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:to="loc_pacb_AptonMember_01a081e7-21ca-7314-8e22-afcfe6192ce1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-76d9-8b28-0549c5b8ebda_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-76d9-8b28-0549c5b8ebda_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TechnologyBasedIntangibleAssetsMember_01a081e7-21ca-7aa7-a29d-48fc075ba96c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TechnologyBasedIntangibleAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:to="loc_us-gaap_TechnologyBasedIntangibleAssetsMember_01a081e7-21ca-7aa7-a29d-48fc075ba96c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LicenseMember_01a081e7-21ca-7b5d-a071-9d429470f92f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LicenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:to="loc_us-gaap_LicenseMember_01a081e7-21ca-7b5d-a071-9d429470f92f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_01a081e7-21ca-76fa-b5b8-f582841d4bea" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_01a081e7-21ca-76fa-b5b8-f582841d4bea" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-78a1-b0e9-1a1aea42fb80_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-78a1-b0e9-1a1aea42fb80_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2025RestructuringMember_01a081e7-21ca-796b-84e9-ac2234a3d703" xlink:href="pacb-20260930.xsd#pacb_A2025RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:to="loc_pacb_A2025RestructuringMember_01a081e7-21ca-796b-84e9-ac2234a3d703" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7331-a487-5a7cce803137_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:to="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7331-a487-5a7cce803137_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:to="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DevelopedTechnologyAndIntellectualPropertyMember_01a081e7-21ca-729b-a2ea-9d1925af62ae" xlink:href="pacb-20260930.xsd#pacb_DevelopedTechnologyAndIntellectualPropertyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:to="loc_pacb_DevelopedTechnologyAndIntellectualPropertyMember_01a081e7-21ca-729b-a2ea-9d1925af62ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-736d-a7da-93a060dfb1e4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-736d-a7da-93a060dfb1e4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InProcessResearchAndDevelopmentMember_01a081e7-21ca-7b6c-913f-143a85c027e8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InProcessResearchAndDevelopmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:to="loc_us-gaap_InProcessResearchAndDevelopmentMember_01a081e7-21ca-7b6c-913f-143a85c027e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7f3b-9534-39857b6ce62b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:to="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7f3b-9534-39857b6ce62b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:to="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseToPatentsAndPatentApplicationsMember_01a081e7-21ca-76dd-9027-ad504f2a9821" xlink:href="pacb-20260930.xsd#pacb_LicenseToPatentsAndPatentApplicationsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:to="loc_pacb_LicenseToPatentsAndPatentApplicationsMember_01a081e7-21ca-76dd-9027-ad504f2a9821" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-78d9-9fc5-a97a8c3a9004_default" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:to="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-78d9-9fc5-a97a8c3a9004_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:to="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScenarioOneMember_01a081e7-21ca-78eb-a95c-503b4ac87a75" xlink:href="pacb-20260930.xsd#pacb_ScenarioOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:to="loc_pacb_ScenarioOneMember_01a081e7-21ca-78eb-a95c-503b4ac87a75" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScenarioTwoMember_01a081e7-21ca-7ab6-a736-23feeb0a7747" xlink:href="pacb-20260930.xsd#pacb_ScenarioTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:to="loc_pacb_ScenarioTwoMember_01a081e7-21ca-7ab6-a736-23feeb0a7747" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementScenarioAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7a41-acb6-29149b789a68_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:to="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7a41-acb6-29149b789a68_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:to="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioForecastMember_01a081e7-21ca-7df9-86ac-2aa2b488f28e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioForecastMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:to="loc_srt_ScenarioForecastMember_01a081e7-21ca-7df9-86ac-2aa2b488f28e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a081e7-21ca-7451-9f34-b8a4e9a6547e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a081e7-21ca-7451-9f34-b8a4e9a6547e" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-7292-91e1-dba03afb6a18_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-7292-91e1-dba03afb6a18_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ServiceMember_01a081e7-21ca-7a04-bc16-96320b74cf9a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ServiceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:to="loc_us-gaap_ServiceMember_01a081e7-21ca-7a04-bc16-96320b74cf9a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillImpairmentLoss_01a081e7-21ca-72d4-a209-177ef2f6dae4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillImpairmentLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_GoodwillImpairmentLoss_01a081e7-21ca-72d4-a209-177ef2f6dae4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets_01a081e7-21ca-7c39-8539-84053b8b71a7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets_01a081e7-21ca-7c39-8539-84053b8b71a7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21ca-728e-94bf-ea2f2b02c81b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillAndIntangibleAssetImpairment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21ca-728e-94bf-ea2f2b02c81b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure_01a081e7-21ca-7c3f-852d-837fabe2b0a0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure_01a081e7-21ca-7c3f-852d-837fabe2b0a0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21ca-7086-8899-66c92344273a" xlink:href="pacb-20260930.xsd#pacb_RestructuringAndRelatedCostAcceleratedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21ca-7086-8899-66c92344273a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_EarningsPerShareNegativeImpactOnNetLossPerShare_01a081e7-21ca-7d8d-a3a0-5361e598fd49" xlink:href="pacb-20260930.xsd#pacb_EarningsPerShareNegativeImpactOnNetLossPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_EarningsPerShareNegativeImpactOnNetLossPerShare_01a081e7-21ca-7d8d-a3a0-5361e598fd49" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionConsiderationTransferred_01a081e7-21ca-79b3-ac02-285c308c42f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionConsiderationTransferred"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_AssetAcquisitionConsiderationTransferred_01a081e7-21ca-79b3-ac02-285c308c42f2" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_01a081e7-21ca-7132-890c-043a9ab4b0c6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_01a081e7-21ca-7132-890c-043a9ab4b0c6" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear_01a081e7-21ca-7840-9b93-99670fd10b96" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear_01a081e7-21ca-7840-9b93-99670fd10b96" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInNextTwelveMonths_01a081e7-21ca-7cc5-8d91-f84ec4808465" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInNextTwelveMonths"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInNextTwelveMonths_01a081e7-21ca-7cc5-8d91-f84ec4808465" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInSecondYear_01a081e7-21ca-792b-825a-1c57cf6746a4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInSecondYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInSecondYear_01a081e7-21ca-792b-825a-1c57cf6746a4" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInThirdYear_01a081e7-21ca-7371-b934-4eebb83e2a9d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInThirdYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInThirdYear_01a081e7-21ca-7371-b934-4eebb83e2a9d" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_OtherCommitmentsIncreaseInPaymentYearTwo_01a081e7-21ca-7550-8fda-22cab6169a41" xlink:href="pacb-20260930.xsd#pacb_OtherCommitmentsIncreaseInPaymentYearTwo"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_OtherCommitmentsIncreaseInPaymentYearTwo_01a081e7-21ca-7550-8fda-22cab6169a41" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne_01a081e7-21ca-7e7a-aba0-eb6280edcbe7" xlink:href="pacb-20260930.xsd#pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne_01a081e7-21ca-7e7a-aba0-eb6280edcbe7" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetRoyaltyRateUtilizedPercentage_01a081e7-21ca-7798-8fe3-b40d6289f712" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetRoyaltyRateUtilizedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetRoyaltyRateUtilizedPercentage_01a081e7-21ca-7798-8fe3-b40d6289f712" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate_01a081e7-21ca-7c39-b4a6-c7cacded209d" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate_01a081e7-21ca-7c39-b4a6-c7cacded209d" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate_01a081e7-21ca-788f-a090-e93e260b7c1c" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate_01a081e7-21ca-788f-a090-e93e260b7c1c" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementConsiderationCapitalized_01a081e7-21ca-72d8-b2f7-2995ecad7468" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementConsiderationCapitalized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementConsiderationCapitalized_01a081e7-21ca-72d8-b2f7-2995ecad7468" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementAmortizationPeriod_01a1a70d-d1ed-7d40-9e5d-052ad4093967" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementAmortizationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementAmortizationPeriod_01a1a70d-d1ed-7d40-9e5d-052ad4093967" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SettlementCharges_01a081e7-21ca-7c48-ad6e-ce4388b38a7b" xlink:href="pacb-20260930.xsd#pacb_SettlementCharges"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_SettlementCharges_01a081e7-21ca-7c48-ad6e-ce4388b38a7b" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementFairValueOfLiability_01a081e7-21ca-7e61-946f-9a818816ed3f" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementFairValueOfLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementFairValueOfLiability_01a081e7-21ca-7e61-946f-9a818816ed3f" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate_01a081e7-21ca-7fc9-b18e-e20ebfc53baf" xlink:href="pacb-20260930.xsd#pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate_01a081e7-21ca-7fc9-b18e-e20ebfc53baf" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrentAndNoncurrent_01a081e7-21ca-7ec3-82c3-eaf577fcfcf7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccruedLiabilitiesCurrentAndNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrentAndNoncurrent_01a081e7-21ca-7ec3-82c3-eaf577fcfcf7" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_01a081e7-21ca-7911-8592-99548c02a09f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_01a081e7-21ca-7911-8592-99548c02a09f" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_01a081e7-21ca-70a5-bfab-82160b3dd1db" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiability_01a081e7-21ca-70a5-bfab-82160b3dd1db" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_01a081e7-21ca-768a-9e1d-40f9ccd72022" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_01a081e7-21ca-768a-9e1d-40f9ccd72022" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_01a081e7-21ca-77f7-ba20-74ee25682aab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_01a081e7-21ca-77f7-ba20-74ee25682aab" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod_01a081e7-21ca-721b-85d9-90670562613e" xlink:href="pacb-20260930.xsd#pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod_01a081e7-21ca-721b-85d9-90670562613e" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_01a081e7-21ca-71fc-8a56-bd1e00992689" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_01a081e7-21ca-71fc-8a56-bd1e00992689" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_01a081e7-21ca-7797-ba5b-e41d07a7822a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_01a081e7-21ca-7797-ba5b-e41d07a7822a" xlink:type="arc" order="29"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_01a081e7-21ca-7816-822b-d7988a1f1646" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligationPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_01a081e7-21ca-7816-822b-d7988a1f1646" xlink:type="arc" order="30"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_01a081e7-21ca-7670-993a-6b06985a9f56" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_01a081e7-21ca-7670-993a-6b06985a9f56" xlink:type="arc" order="31"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_StandardProductWarrantyPeriod_01a081e7-21ca-7fa5-9efa-026dbed12080" xlink:href="pacb-20260930.xsd#pacb_StandardProductWarrantyPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_StandardProductWarrantyPeriod_01a081e7-21ca-7fa5-9efa-026dbed12080" xlink:type="arc" order="32"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/BALANCESHEETCOMPONENTSNarrativeDetails_1" xlink:type="simple" xlink:href="pacb-20260930.xsd#BALANCESHEETCOMPONENTSNarrativeDetails_1"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/BALANCESHEETCOMPONENTSNarrativeDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:href="pacb-20260930.xsd#pacb_ScheduleOfBalanceSheetComponentsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:href="pacb-20260930.xsd#pacb_ScheduleOfBalanceSheetComponentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7b66-a33c-ba05b55f365c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7b66-a33c-ba05b55f365c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_AptonMember_01a081e7-21ca-7314-8e22-afcfe6192ce1" xlink:href="pacb-20260930.xsd#pacb_AptonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:to="loc_pacb_AptonMember_01a081e7-21ca-7314-8e22-afcfe6192ce1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-76d9-8b28-0549c5b8ebda_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-76d9-8b28-0549c5b8ebda_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TechnologyBasedIntangibleAssetsMember_01a081e7-21ca-7aa7-a29d-48fc075ba96c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TechnologyBasedIntangibleAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:to="loc_us-gaap_TechnologyBasedIntangibleAssetsMember_01a081e7-21ca-7aa7-a29d-48fc075ba96c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LicenseMember_01a081e7-21ca-7b5d-a071-9d429470f92f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LicenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:to="loc_us-gaap_LicenseMember_01a081e7-21ca-7b5d-a071-9d429470f92f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-78a1-b0e9-1a1aea42fb80_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-78a1-b0e9-1a1aea42fb80_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2025RestructuringMember_01a081e7-21ca-796b-84e9-ac2234a3d703" xlink:href="pacb-20260930.xsd#pacb_A2025RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:to="loc_pacb_A2025RestructuringMember_01a081e7-21ca-796b-84e9-ac2234a3d703" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7331-a487-5a7cce803137_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:to="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7331-a487-5a7cce803137_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:to="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DevelopedTechnologyAndIntellectualPropertyMember_01a081e7-21ca-729b-a2ea-9d1925af62ae" xlink:href="pacb-20260930.xsd#pacb_DevelopedTechnologyAndIntellectualPropertyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:to="loc_pacb_DevelopedTechnologyAndIntellectualPropertyMember_01a081e7-21ca-729b-a2ea-9d1925af62ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-736d-a7da-93a060dfb1e4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-736d-a7da-93a060dfb1e4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InProcessResearchAndDevelopmentMember_01a081e7-21ca-7b6c-913f-143a85c027e8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InProcessResearchAndDevelopmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:to="loc_us-gaap_InProcessResearchAndDevelopmentMember_01a081e7-21ca-7b6c-913f-143a85c027e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7f3b-9534-39857b6ce62b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:to="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7f3b-9534-39857b6ce62b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:to="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseToPatentsAndPatentApplicationsMember_01a081e7-21ca-76dd-9027-ad504f2a9821" xlink:href="pacb-20260930.xsd#pacb_LicenseToPatentsAndPatentApplicationsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:to="loc_pacb_LicenseToPatentsAndPatentApplicationsMember_01a081e7-21ca-76dd-9027-ad504f2a9821" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-78d9-9fc5-a97a8c3a9004_default" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:to="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-78d9-9fc5-a97a8c3a9004_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:to="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScenarioOneMember_01a081e7-21ca-78eb-a95c-503b4ac87a75" xlink:href="pacb-20260930.xsd#pacb_ScenarioOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:to="loc_pacb_ScenarioOneMember_01a081e7-21ca-78eb-a95c-503b4ac87a75" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScenarioTwoMember_01a081e7-21ca-7ab6-a736-23feeb0a7747" xlink:href="pacb-20260930.xsd#pacb_ScenarioTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:to="loc_pacb_ScenarioTwoMember_01a081e7-21ca-7ab6-a736-23feeb0a7747" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementScenarioAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7a41-acb6-29149b789a68_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:to="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7a41-acb6-29149b789a68_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:to="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioForecastMember_01a081e7-21ca-7df9-86ac-2aa2b488f28e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioForecastMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:to="loc_srt_ScenarioForecastMember_01a081e7-21ca-7df9-86ac-2aa2b488f28e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-7292-91e1-dba03afb6a18_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-7292-91e1-dba03afb6a18_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ServiceMember_01a081e7-21ca-7a04-bc16-96320b74cf9a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ServiceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:to="loc_us-gaap_ServiceMember_01a081e7-21ca-7a04-bc16-96320b74cf9a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillImpairmentLoss_01a081e7-21ca-72d4-a209-177ef2f6dae4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillImpairmentLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_GoodwillImpairmentLoss_01a081e7-21ca-72d4-a209-177ef2f6dae4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets_01a081e7-21ca-7c39-8539-84053b8b71a7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets_01a081e7-21ca-7c39-8539-84053b8b71a7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21ca-728e-94bf-ea2f2b02c81b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillAndIntangibleAssetImpairment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21ca-728e-94bf-ea2f2b02c81b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure_01a081e7-21ca-7c3f-852d-837fabe2b0a0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure_01a081e7-21ca-7c3f-852d-837fabe2b0a0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21ca-7086-8899-66c92344273a" xlink:href="pacb-20260930.xsd#pacb_RestructuringAndRelatedCostAcceleratedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21ca-7086-8899-66c92344273a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_EarningsPerShareNegativeImpactOnNetLossPerShare_01a081e7-21ca-7d8d-a3a0-5361e598fd49" xlink:href="pacb-20260930.xsd#pacb_EarningsPerShareNegativeImpactOnNetLossPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_EarningsPerShareNegativeImpactOnNetLossPerShare_01a081e7-21ca-7d8d-a3a0-5361e598fd49" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionConsiderationTransferred_01a081e7-21ca-79b3-ac02-285c308c42f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionConsiderationTransferred"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_AssetAcquisitionConsiderationTransferred_01a081e7-21ca-79b3-ac02-285c308c42f2" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_01a081e7-21ca-7132-890c-043a9ab4b0c6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_01a081e7-21ca-7132-890c-043a9ab4b0c6" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear_01a081e7-21ca-7840-9b93-99670fd10b96" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear_01a081e7-21ca-7840-9b93-99670fd10b96" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInNextTwelveMonths_01a081e7-21ca-7cc5-8d91-f84ec4808465" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInNextTwelveMonths"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInNextTwelveMonths_01a081e7-21ca-7cc5-8d91-f84ec4808465" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInSecondYear_01a081e7-21ca-792b-825a-1c57cf6746a4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInSecondYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInSecondYear_01a081e7-21ca-792b-825a-1c57cf6746a4" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInThirdYear_01a081e7-21ca-7371-b934-4eebb83e2a9d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInThirdYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInThirdYear_01a081e7-21ca-7371-b934-4eebb83e2a9d" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_OtherCommitmentsIncreaseInPaymentYearTwo_01a081e7-21ca-7550-8fda-22cab6169a41" xlink:href="pacb-20260930.xsd#pacb_OtherCommitmentsIncreaseInPaymentYearTwo"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_OtherCommitmentsIncreaseInPaymentYearTwo_01a081e7-21ca-7550-8fda-22cab6169a41" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne_01a081e7-21ca-7e7a-aba0-eb6280edcbe7" xlink:href="pacb-20260930.xsd#pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne_01a081e7-21ca-7e7a-aba0-eb6280edcbe7" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetRoyaltyRateUtilizedPercentage_01a081e7-21ca-7798-8fe3-b40d6289f712" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetRoyaltyRateUtilizedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetRoyaltyRateUtilizedPercentage_01a081e7-21ca-7798-8fe3-b40d6289f712" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate_01a081e7-21ca-7c39-b4a6-c7cacded209d" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate_01a081e7-21ca-7c39-b4a6-c7cacded209d" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate_01a081e7-21ca-788f-a090-e93e260b7c1c" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate_01a081e7-21ca-788f-a090-e93e260b7c1c" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementConsiderationCapitalized_01a081e7-21ca-72d8-b2f7-2995ecad7468" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementConsiderationCapitalized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementConsiderationCapitalized_01a081e7-21ca-72d8-b2f7-2995ecad7468" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementAmortizationPeriod_01a1a70d-d1ed-7d40-9e5d-052ad4093967" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementAmortizationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementAmortizationPeriod_01a1a70d-d1ed-7d40-9e5d-052ad4093967" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SettlementCharges_01a081e7-21ca-7c48-ad6e-ce4388b38a7b" xlink:href="pacb-20260930.xsd#pacb_SettlementCharges"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_SettlementCharges_01a081e7-21ca-7c48-ad6e-ce4388b38a7b" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementFairValueOfLiability_01a081e7-21ca-7e61-946f-9a818816ed3f" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementFairValueOfLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementFairValueOfLiability_01a081e7-21ca-7e61-946f-9a818816ed3f" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate_01a081e7-21ca-7fc9-b18e-e20ebfc53baf" xlink:href="pacb-20260930.xsd#pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate_01a081e7-21ca-7fc9-b18e-e20ebfc53baf" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrentAndNoncurrent_01a081e7-21ca-7ec3-82c3-eaf577fcfcf7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccruedLiabilitiesCurrentAndNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrentAndNoncurrent_01a081e7-21ca-7ec3-82c3-eaf577fcfcf7" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_01a081e7-21ca-7911-8592-99548c02a09f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_01a081e7-21ca-7911-8592-99548c02a09f" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_01a081e7-21ca-70a5-bfab-82160b3dd1db" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiability_01a081e7-21ca-70a5-bfab-82160b3dd1db" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_01a081e7-21ca-768a-9e1d-40f9ccd72022" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_01a081e7-21ca-768a-9e1d-40f9ccd72022" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_01a081e7-21ca-77f7-ba20-74ee25682aab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_01a081e7-21ca-77f7-ba20-74ee25682aab" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod_01a081e7-21ca-721b-85d9-90670562613e" xlink:href="pacb-20260930.xsd#pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod_01a081e7-21ca-721b-85d9-90670562613e" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_01a081e7-21ca-71fc-8a56-bd1e00992689" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_01a081e7-21ca-71fc-8a56-bd1e00992689" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_01a081e7-21ca-7797-ba5b-e41d07a7822a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_01a081e7-21ca-7797-ba5b-e41d07a7822a" xlink:type="arc" order="29"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_01a081e7-21ca-7816-822b-d7988a1f1646" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligationPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_01a081e7-21ca-7816-822b-d7988a1f1646" xlink:type="arc" order="30"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_01a081e7-21ca-7670-993a-6b06985a9f56" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_01a081e7-21ca-7670-993a-6b06985a9f56" xlink:type="arc" order="31"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_StandardProductWarrantyPeriod_01a081e7-21ca-7fa5-9efa-026dbed12080" xlink:href="pacb-20260930.xsd#pacb_StandardProductWarrantyPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_StandardProductWarrantyPeriod_01a081e7-21ca-7fa5-9efa-026dbed12080" xlink:type="arc" order="32"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/BALANCESHEETCOMPONENTSNarrativeDetails_2" xlink:type="simple" xlink:href="pacb-20260930.xsd#BALANCESHEETCOMPONENTSNarrativeDetails_2"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/BALANCESHEETCOMPONENTSNarrativeDetails_2" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:href="pacb-20260930.xsd#pacb_ScheduleOfBalanceSheetComponentsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:href="pacb-20260930.xsd#pacb_ScheduleOfBalanceSheetComponentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7b66-a33c-ba05b55f365c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7b66-a33c-ba05b55f365c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_AptonMember_01a081e7-21ca-7314-8e22-afcfe6192ce1" xlink:href="pacb-20260930.xsd#pacb_AptonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:to="loc_pacb_AptonMember_01a081e7-21ca-7314-8e22-afcfe6192ce1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-76d9-8b28-0549c5b8ebda_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-76d9-8b28-0549c5b8ebda_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TechnologyBasedIntangibleAssetsMember_01a081e7-21ca-7aa7-a29d-48fc075ba96c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TechnologyBasedIntangibleAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:to="loc_us-gaap_TechnologyBasedIntangibleAssetsMember_01a081e7-21ca-7aa7-a29d-48fc075ba96c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LicenseMember_01a081e7-21ca-7b5d-a071-9d429470f92f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LicenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:to="loc_us-gaap_LicenseMember_01a081e7-21ca-7b5d-a071-9d429470f92f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-78a1-b0e9-1a1aea42fb80_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-78a1-b0e9-1a1aea42fb80_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2025RestructuringMember_01a081e7-21ca-796b-84e9-ac2234a3d703" xlink:href="pacb-20260930.xsd#pacb_A2025RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:to="loc_pacb_A2025RestructuringMember_01a081e7-21ca-796b-84e9-ac2234a3d703" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7331-a487-5a7cce803137_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:to="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7331-a487-5a7cce803137_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:to="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DevelopedTechnologyAndIntellectualPropertyMember_01a081e7-21ca-729b-a2ea-9d1925af62ae" xlink:href="pacb-20260930.xsd#pacb_DevelopedTechnologyAndIntellectualPropertyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:to="loc_pacb_DevelopedTechnologyAndIntellectualPropertyMember_01a081e7-21ca-729b-a2ea-9d1925af62ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-736d-a7da-93a060dfb1e4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-736d-a7da-93a060dfb1e4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InProcessResearchAndDevelopmentMember_01a081e7-21ca-7b6c-913f-143a85c027e8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InProcessResearchAndDevelopmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:to="loc_us-gaap_InProcessResearchAndDevelopmentMember_01a081e7-21ca-7b6c-913f-143a85c027e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7f3b-9534-39857b6ce62b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:to="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7f3b-9534-39857b6ce62b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:to="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseToPatentsAndPatentApplicationsMember_01a081e7-21ca-76dd-9027-ad504f2a9821" xlink:href="pacb-20260930.xsd#pacb_LicenseToPatentsAndPatentApplicationsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:to="loc_pacb_LicenseToPatentsAndPatentApplicationsMember_01a081e7-21ca-76dd-9027-ad504f2a9821" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-78d9-9fc5-a97a8c3a9004_default" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:to="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-78d9-9fc5-a97a8c3a9004_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:to="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScenarioOneMember_01a081e7-21ca-78eb-a95c-503b4ac87a75" xlink:href="pacb-20260930.xsd#pacb_ScenarioOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:to="loc_pacb_ScenarioOneMember_01a081e7-21ca-78eb-a95c-503b4ac87a75" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScenarioTwoMember_01a081e7-21ca-7ab6-a736-23feeb0a7747" xlink:href="pacb-20260930.xsd#pacb_ScenarioTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:to="loc_pacb_ScenarioTwoMember_01a081e7-21ca-7ab6-a736-23feeb0a7747" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementScenarioAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7a41-acb6-29149b789a68_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:to="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7a41-acb6-29149b789a68_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:to="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioForecastMember_01a081e7-21ca-7df9-86ac-2aa2b488f28e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioForecastMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:to="loc_srt_ScenarioForecastMember_01a081e7-21ca-7df9-86ac-2aa2b488f28e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-7292-91e1-dba03afb6a18_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-7292-91e1-dba03afb6a18_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ServiceMember_01a081e7-21ca-7a04-bc16-96320b74cf9a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ServiceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:to="loc_us-gaap_ServiceMember_01a081e7-21ca-7a04-bc16-96320b74cf9a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_01a081e7-21ca-76fa-b5b8-f582841d4bea" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_01a081e7-21ca-76fa-b5b8-f582841d4bea" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillImpairmentLoss_01a081e7-21ca-72d4-a209-177ef2f6dae4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillImpairmentLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_GoodwillImpairmentLoss_01a081e7-21ca-72d4-a209-177ef2f6dae4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets_01a081e7-21ca-7c39-8539-84053b8b71a7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets_01a081e7-21ca-7c39-8539-84053b8b71a7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21ca-728e-94bf-ea2f2b02c81b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillAndIntangibleAssetImpairment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21ca-728e-94bf-ea2f2b02c81b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure_01a081e7-21ca-7c3f-852d-837fabe2b0a0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure_01a081e7-21ca-7c3f-852d-837fabe2b0a0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21ca-7086-8899-66c92344273a" xlink:href="pacb-20260930.xsd#pacb_RestructuringAndRelatedCostAcceleratedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21ca-7086-8899-66c92344273a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_EarningsPerShareNegativeImpactOnNetLossPerShare_01a081e7-21ca-7d8d-a3a0-5361e598fd49" xlink:href="pacb-20260930.xsd#pacb_EarningsPerShareNegativeImpactOnNetLossPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_EarningsPerShareNegativeImpactOnNetLossPerShare_01a081e7-21ca-7d8d-a3a0-5361e598fd49" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionConsiderationTransferred_01a081e7-21ca-79b3-ac02-285c308c42f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionConsiderationTransferred"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_AssetAcquisitionConsiderationTransferred_01a081e7-21ca-79b3-ac02-285c308c42f2" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_01a081e7-21ca-7132-890c-043a9ab4b0c6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_01a081e7-21ca-7132-890c-043a9ab4b0c6" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear_01a081e7-21ca-7840-9b93-99670fd10b96" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear_01a081e7-21ca-7840-9b93-99670fd10b96" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInNextTwelveMonths_01a081e7-21ca-7cc5-8d91-f84ec4808465" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInNextTwelveMonths"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInNextTwelveMonths_01a081e7-21ca-7cc5-8d91-f84ec4808465" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInSecondYear_01a081e7-21ca-792b-825a-1c57cf6746a4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInSecondYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInSecondYear_01a081e7-21ca-792b-825a-1c57cf6746a4" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInThirdYear_01a081e7-21ca-7371-b934-4eebb83e2a9d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInThirdYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInThirdYear_01a081e7-21ca-7371-b934-4eebb83e2a9d" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_OtherCommitmentsIncreaseInPaymentYearTwo_01a081e7-21ca-7550-8fda-22cab6169a41" xlink:href="pacb-20260930.xsd#pacb_OtherCommitmentsIncreaseInPaymentYearTwo"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_OtherCommitmentsIncreaseInPaymentYearTwo_01a081e7-21ca-7550-8fda-22cab6169a41" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne_01a081e7-21ca-7e7a-aba0-eb6280edcbe7" xlink:href="pacb-20260930.xsd#pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne_01a081e7-21ca-7e7a-aba0-eb6280edcbe7" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetRoyaltyRateUtilizedPercentage_01a081e7-21ca-7798-8fe3-b40d6289f712" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetRoyaltyRateUtilizedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetRoyaltyRateUtilizedPercentage_01a081e7-21ca-7798-8fe3-b40d6289f712" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate_01a081e7-21ca-7c39-b4a6-c7cacded209d" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate_01a081e7-21ca-7c39-b4a6-c7cacded209d" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate_01a081e7-21ca-788f-a090-e93e260b7c1c" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate_01a081e7-21ca-788f-a090-e93e260b7c1c" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementConsiderationCapitalized_01a081e7-21ca-72d8-b2f7-2995ecad7468" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementConsiderationCapitalized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementConsiderationCapitalized_01a081e7-21ca-72d8-b2f7-2995ecad7468" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementAmortizationPeriod_01a1a70d-d1ed-7d40-9e5d-052ad4093967" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementAmortizationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementAmortizationPeriod_01a1a70d-d1ed-7d40-9e5d-052ad4093967" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SettlementCharges_01a081e7-21ca-7c48-ad6e-ce4388b38a7b" xlink:href="pacb-20260930.xsd#pacb_SettlementCharges"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_SettlementCharges_01a081e7-21ca-7c48-ad6e-ce4388b38a7b" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementFairValueOfLiability_01a081e7-21ca-7e61-946f-9a818816ed3f" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementFairValueOfLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementFairValueOfLiability_01a081e7-21ca-7e61-946f-9a818816ed3f" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate_01a081e7-21ca-7fc9-b18e-e20ebfc53baf" xlink:href="pacb-20260930.xsd#pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate_01a081e7-21ca-7fc9-b18e-e20ebfc53baf" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrentAndNoncurrent_01a081e7-21ca-7ec3-82c3-eaf577fcfcf7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccruedLiabilitiesCurrentAndNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrentAndNoncurrent_01a081e7-21ca-7ec3-82c3-eaf577fcfcf7" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_01a081e7-21ca-7911-8592-99548c02a09f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_01a081e7-21ca-7911-8592-99548c02a09f" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_01a081e7-21ca-70a5-bfab-82160b3dd1db" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiability_01a081e7-21ca-70a5-bfab-82160b3dd1db" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_01a081e7-21ca-768a-9e1d-40f9ccd72022" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_01a081e7-21ca-768a-9e1d-40f9ccd72022" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_01a081e7-21ca-77f7-ba20-74ee25682aab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_01a081e7-21ca-77f7-ba20-74ee25682aab" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod_01a081e7-21ca-721b-85d9-90670562613e" xlink:href="pacb-20260930.xsd#pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod_01a081e7-21ca-721b-85d9-90670562613e" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_01a081e7-21ca-71fc-8a56-bd1e00992689" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_01a081e7-21ca-71fc-8a56-bd1e00992689" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_01a081e7-21ca-7797-ba5b-e41d07a7822a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_01a081e7-21ca-7797-ba5b-e41d07a7822a" xlink:type="arc" order="29"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_01a081e7-21ca-7816-822b-d7988a1f1646" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligationPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_01a081e7-21ca-7816-822b-d7988a1f1646" xlink:type="arc" order="30"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_01a081e7-21ca-7670-993a-6b06985a9f56" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_01a081e7-21ca-7670-993a-6b06985a9f56" xlink:type="arc" order="31"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_StandardProductWarrantyPeriod_01a081e7-21ca-7fa5-9efa-026dbed12080" xlink:href="pacb-20260930.xsd#pacb_StandardProductWarrantyPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_StandardProductWarrantyPeriod_01a081e7-21ca-7fa5-9efa-026dbed12080" xlink:type="arc" order="32"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/BALANCESHEETCOMPONENTSNarrativeDetails_3" xlink:type="simple" xlink:href="pacb-20260930.xsd#BALANCESHEETCOMPONENTSNarrativeDetails_3"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/BALANCESHEETCOMPONENTSNarrativeDetails_3" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:href="pacb-20260930.xsd#pacb_ScheduleOfBalanceSheetComponentsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:href="pacb-20260930.xsd#pacb_ScheduleOfBalanceSheetComponentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7b66-a33c-ba05b55f365c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-7b66-a33c-ba05b55f365c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a081e7-21ca-7b66-a33c-ba05b55f365c" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_AptonMember_01a081e7-21ca-7314-8e22-afcfe6192ce1" xlink:href="pacb-20260930.xsd#pacb_AptonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a081e7-21ca-73a0-9d97-8d9f83786822" xlink:to="loc_pacb_AptonMember_01a081e7-21ca-7314-8e22-afcfe6192ce1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-76d9-8b28-0549c5b8ebda_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-76d9-8b28-0549c5b8ebda_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-76d9-8b28-0549c5b8ebda" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TechnologyBasedIntangibleAssetsMember_01a081e7-21ca-7aa7-a29d-48fc075ba96c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TechnologyBasedIntangibleAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:to="loc_us-gaap_TechnologyBasedIntangibleAssetsMember_01a081e7-21ca-7aa7-a29d-48fc075ba96c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LicenseMember_01a081e7-21ca-7b5d-a071-9d429470f92f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LicenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cc2-b6c7-88aaae60336d" xlink:to="loc_us-gaap_LicenseMember_01a081e7-21ca-7b5d-a071-9d429470f92f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-78a1-b0e9-1a1aea42fb80_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-78a1-b0e9-1a1aea42fb80_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21ca-78a1-b0e9-1a1aea42fb80" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2025RestructuringMember_01a081e7-21ca-796b-84e9-ac2234a3d703" xlink:href="pacb-20260930.xsd#pacb_A2025RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21ca-7a75-91f8-92340e3680a0" xlink:to="loc_pacb_A2025RestructuringMember_01a081e7-21ca-796b-84e9-ac2234a3d703" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7331-a487-5a7cce803137_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:to="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7331-a487-5a7cce803137_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetAcquisitionAxis_01a081e7-21ca-7331-a487-5a7cce803137" xlink:to="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DevelopedTechnologyAndIntellectualPropertyMember_01a081e7-21ca-729b-a2ea-9d1925af62ae" xlink:href="pacb-20260930.xsd#pacb_DevelopedTechnologyAndIntellectualPropertyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionDomain_01a081e7-21ca-7a64-ae6a-c2bb4ffff6a4" xlink:to="loc_pacb_DevelopedTechnologyAndIntellectualPropertyMember_01a081e7-21ca-729b-a2ea-9d1925af62ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-736d-a7da-93a060dfb1e4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-736d-a7da-93a060dfb1e4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-736d-a7da-93a060dfb1e4" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InProcessResearchAndDevelopmentMember_01a081e7-21ca-7b6c-913f-143a85c027e8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InProcessResearchAndDevelopmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-721d-93e9-e980afe92c02" xlink:to="loc_us-gaap_InProcessResearchAndDevelopmentMember_01a081e7-21ca-7b6c-913f-143a85c027e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7f3b-9534-39857b6ce62b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:to="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7f3b-9534-39857b6ce62b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_OtherCommitmentsAxis_01a081e7-21ca-7f3b-9534-39857b6ce62b" xlink:to="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseToPatentsAndPatentApplicationsMember_01a081e7-21ca-76dd-9027-ad504f2a9821" xlink:href="pacb-20260930.xsd#pacb_LicenseToPatentsAndPatentApplicationsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsDomain_01a081e7-21ca-7c16-8f12-2f0c54e450bd" xlink:to="loc_pacb_LicenseToPatentsAndPatentApplicationsMember_01a081e7-21ca-76dd-9027-ad504f2a9821" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-78d9-9fc5-a97a8c3a9004_default" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:to="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-78d9-9fc5-a97a8c3a9004_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:href="pacb-20260930.xsd#pacb_SequenceOfEventsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_pacb_SequenceOfEventsAxis_01a081e7-21ca-78d9-9fc5-a97a8c3a9004" xlink:to="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScenarioOneMember_01a081e7-21ca-78eb-a95c-503b4ac87a75" xlink:href="pacb-20260930.xsd#pacb_ScenarioOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:to="loc_pacb_ScenarioOneMember_01a081e7-21ca-78eb-a95c-503b4ac87a75" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ScenarioTwoMember_01a081e7-21ca-7ab6-a736-23feeb0a7747" xlink:href="pacb-20260930.xsd#pacb_ScenarioTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_SequenceOfEventsDomain_01a081e7-21ca-70b8-8cd8-f66dd896d68e" xlink:to="loc_pacb_ScenarioTwoMember_01a081e7-21ca-7ab6-a736-23feeb0a7747" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementScenarioAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7a41-acb6-29149b789a68_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:to="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7a41-acb6-29149b789a68_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementScenarioAxis_01a081e7-21ca-7a41-acb6-29149b789a68" xlink:to="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioForecastMember_01a081e7-21ca-7df9-86ac-2aa2b488f28e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioForecastMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ScenarioUnspecifiedDomain_01a081e7-21ca-7e7b-8a3c-ec5917c9a903" xlink:to="loc_srt_ScenarioForecastMember_01a081e7-21ca-7df9-86ac-2aa2b488f28e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-7292-91e1-dba03afb6a18_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-7292-91e1-dba03afb6a18_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21ca-7292-91e1-dba03afb6a18" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ServiceMember_01a081e7-21ca-7a04-bc16-96320b74cf9a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ServiceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a081e7-21ca-73b2-995d-22e062df83fc" xlink:to="loc_us-gaap_ServiceMember_01a081e7-21ca-7a04-bc16-96320b74cf9a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a081e7-21ca-7451-9f34-b8a4e9a6547e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsTable_01a081e7-21ca-7bdb-948f-2436a9c7d230" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a081e7-21ca-7451-9f34-b8a4e9a6547e" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillImpairmentLoss_01a081e7-21ca-72d4-a209-177ef2f6dae4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillImpairmentLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_GoodwillImpairmentLoss_01a081e7-21ca-72d4-a209-177ef2f6dae4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets_01a081e7-21ca-7c39-8539-84053b8b71a7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets_01a081e7-21ca-7c39-8539-84053b8b71a7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21ca-728e-94bf-ea2f2b02c81b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillAndIntangibleAssetImpairment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21ca-728e-94bf-ea2f2b02c81b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure_01a081e7-21ca-7c3f-852d-837fabe2b0a0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure_01a081e7-21ca-7c3f-852d-837fabe2b0a0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21ca-7086-8899-66c92344273a" xlink:href="pacb-20260930.xsd#pacb_RestructuringAndRelatedCostAcceleratedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21ca-7086-8899-66c92344273a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_EarningsPerShareNegativeImpactOnNetLossPerShare_01a081e7-21ca-7d8d-a3a0-5361e598fd49" xlink:href="pacb-20260930.xsd#pacb_EarningsPerShareNegativeImpactOnNetLossPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_EarningsPerShareNegativeImpactOnNetLossPerShare_01a081e7-21ca-7d8d-a3a0-5361e598fd49" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionConsiderationTransferred_01a081e7-21ca-79b3-ac02-285c308c42f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionConsiderationTransferred"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_AssetAcquisitionConsiderationTransferred_01a081e7-21ca-79b3-ac02-285c308c42f2" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_01a081e7-21ca-7132-890c-043a9ab4b0c6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_01a081e7-21ca-7132-890c-043a9ab4b0c6" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear_01a081e7-21ca-7840-9b93-99670fd10b96" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentsFutureMinimumPaymentsRemainderOfFiscalYear_01a081e7-21ca-7840-9b93-99670fd10b96" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInNextTwelveMonths_01a081e7-21ca-7cc5-8d91-f84ec4808465" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInNextTwelveMonths"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInNextTwelveMonths_01a081e7-21ca-7cc5-8d91-f84ec4808465" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInSecondYear_01a081e7-21ca-792b-825a-1c57cf6746a4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInSecondYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInSecondYear_01a081e7-21ca-792b-825a-1c57cf6746a4" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentDueInThirdYear_01a081e7-21ca-7371-b934-4eebb83e2a9d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentDueInThirdYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherCommitmentDueInThirdYear_01a081e7-21ca-7371-b934-4eebb83e2a9d" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_OtherCommitmentsIncreaseInPaymentYearTwo_01a081e7-21ca-7550-8fda-22cab6169a41" xlink:href="pacb-20260930.xsd#pacb_OtherCommitmentsIncreaseInPaymentYearTwo"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_OtherCommitmentsIncreaseInPaymentYearTwo_01a081e7-21ca-7550-8fda-22cab6169a41" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne_01a081e7-21ca-7e7a-aba0-eb6280edcbe7" xlink:href="pacb-20260930.xsd#pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_OtherCommitmentCovenantMinimumRevenueMarkerYearOne_01a081e7-21ca-7e7a-aba0-eb6280edcbe7" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetRoyaltyRateUtilizedPercentage_01a081e7-21ca-7798-8fe3-b40d6289f712" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetRoyaltyRateUtilizedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetRoyaltyRateUtilizedPercentage_01a081e7-21ca-7798-8fe3-b40d6289f712" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate_01a081e7-21ca-7c39-b4a6-c7cacded209d" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetRoyaltyRateUtilizedDiscountRate_01a081e7-21ca-7c39-b4a6-c7cacded209d" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate_01a081e7-21ca-788f-a090-e93e260b7c1c" xlink:href="pacb-20260930.xsd#pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_IntangibleAssetWeightedAverageCostOfCapitalDiscountRate_01a081e7-21ca-788f-a090-e93e260b7c1c" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementConsiderationCapitalized_01a081e7-21ca-72d8-b2f7-2995ecad7468" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementConsiderationCapitalized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementConsiderationCapitalized_01a081e7-21ca-72d8-b2f7-2995ecad7468" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementAmortizationPeriod_01a1a70d-d1ed-7d40-9e5d-052ad4093967" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementAmortizationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementAmortizationPeriod_01a1a70d-d1ed-7d40-9e5d-052ad4093967" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SettlementCharges_01a081e7-21ca-7c48-ad6e-ce4388b38a7b" xlink:href="pacb-20260930.xsd#pacb_SettlementCharges"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_SettlementCharges_01a081e7-21ca-7c48-ad6e-ce4388b38a7b" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_LicenseAgreementFairValueOfLiability_01a081e7-21ca-7e61-946f-9a818816ed3f" xlink:href="pacb-20260930.xsd#pacb_LicenseAgreementFairValueOfLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_LicenseAgreementFairValueOfLiability_01a081e7-21ca-7e61-946f-9a818816ed3f" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate_01a081e7-21ca-7fc9-b18e-e20ebfc53baf" xlink:href="pacb-20260930.xsd#pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_UndiscountedEffectiveInterestMethodEffectiveInterestRate_01a081e7-21ca-7fc9-b18e-e20ebfc53baf" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrentAndNoncurrent_01a081e7-21ca-7ec3-82c3-eaf577fcfcf7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccruedLiabilitiesCurrentAndNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrentAndNoncurrent_01a081e7-21ca-7ec3-82c3-eaf577fcfcf7" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_01a081e7-21ca-7911-8592-99548c02a09f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_01a081e7-21ca-7911-8592-99548c02a09f" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_01a081e7-21ca-70a5-bfab-82160b3dd1db" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiability_01a081e7-21ca-70a5-bfab-82160b3dd1db" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_01a081e7-21ca-768a-9e1d-40f9ccd72022" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_01a081e7-21ca-768a-9e1d-40f9ccd72022" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_01a081e7-21ca-77f7-ba20-74ee25682aab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_01a081e7-21ca-77f7-ba20-74ee25682aab" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod_01a081e7-21ca-721b-85d9-90670562613e" xlink:href="pacb-20260930.xsd#pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod_01a081e7-21ca-721b-85d9-90670562613e" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_01a081e7-21ca-71fc-8a56-bd1e00992689" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_01a081e7-21ca-71fc-8a56-bd1e00992689" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_01a081e7-21ca-7797-ba5b-e41d07a7822a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_01a081e7-21ca-7797-ba5b-e41d07a7822a" xlink:type="arc" order="29"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_01a081e7-21ca-7816-822b-d7988a1f1646" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligationPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_01a081e7-21ca-7816-822b-d7988a1f1646" xlink:type="arc" order="30"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_01a081e7-21ca-7670-993a-6b06985a9f56" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_01a081e7-21ca-7670-993a-6b06985a9f56" xlink:type="arc" order="31"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_StandardProductWarrantyPeriod_01a081e7-21ca-7fa5-9efa-026dbed12080" xlink:href="pacb-20260930.xsd#pacb_StandardProductWarrantyPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_ScheduleOfBalanceSheetComponentsLineItems_01a081e7-21ca-72db-8b61-ffa1c4cfcbd9" xlink:to="loc_pacb_StandardProductWarrantyPeriod_01a081e7-21ca-7fa5-9efa-026dbed12080" xlink:type="arc" order="32"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/BALANCESHEETCOMPONENTSScheduleofFiniteLivedIntangibleAssetsFromBusinessAcquisitionsDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#BALANCESHEETCOMPONENTSScheduleofFiniteLivedIntangibleAssetsFromBusinessAcquisitionsDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/BALANCESHEETCOMPONENTSScheduleofFiniteLivedIntangibleAssetsFromBusinessAcquisitionsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a081e7-21ca-7ec3-8db2-9c32c83867b6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a081e7-21ca-7e67-8ee3-23b8256bea4d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a081e7-21ca-7ec3-8db2-9c32c83867b6" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a081e7-21ca-7e67-8ee3-23b8256bea4d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-788f-8299-1f4bd75c193b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a081e7-21ca-7e67-8ee3-23b8256bea4d" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-788f-8299-1f4bd75c193b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-788f-8299-1f4bd75c193b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-788f-8299-1f4bd75c193b" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-788f-8299-1f4bd75c193b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cf5-97a5-395626e7f285" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21ca-788f-8299-1f4bd75c193b" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cf5-97a5-395626e7f285" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SoftwareDevelopmentMember_01a081e7-21ca-7990-a039-39fe70b49afc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SoftwareDevelopmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cf5-97a5-395626e7f285" xlink:to="loc_us-gaap_SoftwareDevelopmentMember_01a081e7-21ca-7990-a039-39fe70b49afc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerRelationshipsMember_01a081e7-21ca-72a1-a5b6-d1c567d684f8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CustomerRelationshipsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21ca-7cf5-97a5-395626e7f285" xlink:to="loc_us-gaap_CustomerRelationshipsMember_01a081e7-21ca-72a1-a5b6-d1c567d684f8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a081e7-21ca-700d-bd5a-36f6926f2501" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a081e7-21ca-7e67-8ee3-23b8256bea4d" xlink:to="loc_srt_RangeAxis_01a081e7-21ca-700d-bd5a-36f6926f2501" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a081e7-21ca-700d-bd5a-36f6926f2501_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a081e7-21ca-700d-bd5a-36f6926f2501" xlink:to="loc_srt_RangeMember_01a081e7-21ca-700d-bd5a-36f6926f2501_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a081e7-21ca-7455-8b6d-af811d194fc6" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a081e7-21ca-700d-bd5a-36f6926f2501" xlink:to="loc_srt_RangeMember_01a081e7-21ca-7455-8b6d-af811d194fc6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_01a081e7-21ca-7d3a-9512-7f96f537cd93" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a081e7-21ca-7455-8b6d-af811d194fc6" xlink:to="loc_srt_MinimumMember_01a081e7-21ca-7d3a-9512-7f96f537cd93" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_01a081e7-21ca-7a03-8d3a-78f6aaccd355" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a081e7-21ca-7455-8b6d-af811d194fc6" xlink:to="loc_srt_MaximumMember_01a081e7-21ca-7a03-8d3a-78f6aaccd355" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_01a081e7-21ca-7e33-bc00-70109e836005" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a081e7-21ca-7ec3-8db2-9c32c83867b6" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_01a081e7-21ca-7e33-bc00-70109e836005" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_01a081e7-21ca-7d8c-a7c0-bb07353c4b56" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a081e7-21ca-7ec3-8db2-9c32c83867b6" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_01a081e7-21ca-7d8c-a7c0-bb07353c4b56" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_01a081e7-21ca-722b-8087-4ce9939b221e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a081e7-21ca-7ec3-8db2-9c32c83867b6" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_01a081e7-21ca-722b-8087-4ce9939b221e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_01a081e7-21ca-7947-9c25-6eddd03454ae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a081e7-21ca-7ec3-8db2-9c32c83867b6" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_01a081e7-21ca-7947-9c25-6eddd03454ae" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/CONVERTIBLESENIORNOTESNarrativeDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#CONVERTIBLESENIORNOTESNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/CONVERTIBLESENIORNOTESNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-79db-8c84-0da739e338a3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-79db-8c84-0da739e338a3" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7f7e-96b5-4da28fb3b277" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-79db-8c84-0da739e338a3" xlink:to="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7f7e-96b5-4da28fb3b277" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7f7e-96b5-4da28fb3b277_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7f7e-96b5-4da28fb3b277" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7f7e-96b5-4da28fb3b277_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-787d-aba7-1c4d00c19e3f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7f7e-96b5-4da28fb3b277" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-787d-aba7-1c4d00c19e3f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2028ConvertibleSeniorNotesMember_01a081e7-21ca-72d7-8f46-9a626aae8c4b" xlink:href="pacb-20260930.xsd#pacb_A2028ConvertibleSeniorNotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-787d-aba7-1c4d00c19e3f" xlink:to="loc_pacb_A2028ConvertibleSeniorNotesMember_01a081e7-21ca-72d7-8f46-9a626aae8c4b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2029NotesMember_01a081e7-21ca-769d-87bb-10bf8f701f75" xlink:href="pacb-20260930.xsd#pacb_A2029NotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-787d-aba7-1c4d00c19e3f" xlink:to="loc_pacb_A2029NotesMember_01a081e7-21ca-769d-87bb-10bf8f701f75" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ExchangeTransactionMember_01a081e7-21ca-7ab3-8adc-6caba18fe2e6" xlink:href="pacb-20260930.xsd#pacb_ExchangeTransactionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-787d-aba7-1c4d00c19e3f" xlink:to="loc_pacb_ExchangeTransactionMember_01a081e7-21ca-7ab3-8adc-6caba18fe2e6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2030ConvertibleSeniorNotesMember_01a081e7-21ca-7d5e-ae09-a419f9174fad" xlink:href="pacb-20260930.xsd#pacb_A2030ConvertibleSeniorNotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-787d-aba7-1c4d00c19e3f" xlink:to="loc_pacb_A2030ConvertibleSeniorNotesMember_01a081e7-21ca-7d5e-ae09-a419f9174fad" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_01a081e7-21ca-79e6-a4df-d95106584e17" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-79db-8c84-0da739e338a3" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_01a081e7-21ca-79e6-a4df-d95106584e17" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_01a081e7-21ca-79e6-a4df-d95106584e17_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_01a081e7-21ca-79e6-a4df-d95106584e17" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_01a081e7-21ca-79e6-a4df-d95106584e17_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_01a081e7-21ca-7357-b8b4-67cb7d1aad9d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_01a081e7-21ca-79e6-a4df-d95106584e17" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_01a081e7-21ca-7357-b8b4-67cb7d1aad9d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_01a081e7-21ca-7145-9d1a-f3b4e26626c4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_01a081e7-21ca-7357-b8b4-67cb7d1aad9d" xlink:to="loc_us-gaap_ConvertibleDebtMember_01a081e7-21ca-7145-9d1a-f3b4e26626c4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_01a081e7-21ca-7226-901d-ad19ae83fc23" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-79db-8c84-0da739e338a3" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_01a081e7-21ca-7226-901d-ad19ae83fc23" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_01a081e7-21ca-7226-901d-ad19ae83fc23_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_01a081e7-21ca-7226-901d-ad19ae83fc23" xlink:to="loc_us-gaap_RelatedPartyDomain_01a081e7-21ca-7226-901d-ad19ae83fc23_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_01a081e7-21ca-7b10-9dca-10d1fa0e5d3a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_01a081e7-21ca-7226-901d-ad19ae83fc23" xlink:to="loc_us-gaap_RelatedPartyDomain_01a081e7-21ca-7b10-9dca-10d1fa0e5d3a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_AffiliatedEntityMember_01a081e7-21ca-76b4-bb19-0ddd008ca862" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_AffiliatedEntityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_01a081e7-21ca-7b10-9dca-10d1fa0e5d3a" xlink:to="loc_srt_AffiliatedEntityMember_01a081e7-21ca-76b4-bb19-0ddd008ca862" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtInstrumentConvertibleTermsOfConversionAxis_01a081e7-21ca-7e6a-bb57-3aac05c8e662" xlink:href="pacb-20260930.xsd#pacb_DebtInstrumentConvertibleTermsOfConversionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-79db-8c84-0da739e338a3" xlink:to="loc_pacb_DebtInstrumentConvertibleTermsOfConversionAxis_01a081e7-21ca-7e6a-bb57-3aac05c8e662" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtInstrumentConvertibleTermsOfConversionDomain_01a081e7-21ca-7e6a-bb57-3aac05c8e662_default" xlink:href="pacb-20260930.xsd#pacb_DebtInstrumentConvertibleTermsOfConversionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_pacb_DebtInstrumentConvertibleTermsOfConversionAxis_01a081e7-21ca-7e6a-bb57-3aac05c8e662" xlink:to="loc_pacb_DebtInstrumentConvertibleTermsOfConversionDomain_01a081e7-21ca-7e6a-bb57-3aac05c8e662_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtInstrumentConvertibleTermsOfConversionDomain_01a081e7-21ca-7e43-a52f-20561351ee78" xlink:href="pacb-20260930.xsd#pacb_DebtInstrumentConvertibleTermsOfConversionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_pacb_DebtInstrumentConvertibleTermsOfConversionAxis_01a081e7-21ca-7e6a-bb57-3aac05c8e662" xlink:to="loc_pacb_DebtInstrumentConvertibleTermsOfConversionDomain_01a081e7-21ca-7e43-a52f-20561351ee78" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtConversionTermsOneMember_01a081e7-21ca-77ee-97e7-1bcc37d4991b" xlink:href="pacb-20260930.xsd#pacb_DebtConversionTermsOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_DebtInstrumentConvertibleTermsOfConversionDomain_01a081e7-21ca-7e43-a52f-20561351ee78" xlink:to="loc_pacb_DebtConversionTermsOneMember_01a081e7-21ca-77ee-97e7-1bcc37d4991b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtConversionTermsTwoMember_01a081e7-21ca-7380-9567-7e7babfc9cbb" xlink:href="pacb-20260930.xsd#pacb_DebtConversionTermsTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_pacb_DebtInstrumentConvertibleTermsOfConversionDomain_01a081e7-21ca-7e43-a52f-20561351ee78" xlink:to="loc_pacb_DebtConversionTermsTwoMember_01a081e7-21ca-7380-9567-7e7babfc9cbb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a081e7-21ca-791d-872a-bf958f535773" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-79db-8c84-0da739e338a3" xlink:to="loc_srt_RangeAxis_01a081e7-21ca-791d-872a-bf958f535773" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a081e7-21ca-791d-872a-bf958f535773_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a081e7-21ca-791d-872a-bf958f535773" xlink:to="loc_srt_RangeMember_01a081e7-21ca-791d-872a-bf958f535773_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a081e7-21ca-72e6-b4f1-3ba4ae201e37" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a081e7-21ca-791d-872a-bf958f535773" xlink:to="loc_srt_RangeMember_01a081e7-21ca-72e6-b4f1-3ba4ae201e37" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_01a081e7-21ca-724e-89ec-c02c368d3ac8" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a081e7-21ca-72e6-b4f1-3ba4ae201e37" xlink:to="loc_srt_MinimumMember_01a081e7-21ca-724e-89ec-c02c368d3ac8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_01a081e7-21ca-7bd2-ba47-96d7eb6e5630" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a081e7-21ca-72e6-b4f1-3ba4ae201e37" xlink:to="loc_srt_MaximumMember_01a081e7-21ca-7bd2-ba47-96d7eb6e5630" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_01a081e7-21ca-7b76-8510-c8a42e82a6cb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_01a081e7-21ca-7b76-8510-c8a42e82a6cb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_01a081e7-21ca-70bc-8ac0-67a2a7489a78" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_01a081e7-21ca-70bc-8ac0-67a2a7489a78" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_01a081e7-21ca-70ba-9cdf-183f955dff02" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_01a081e7-21ca-70ba-9cdf-183f955dff02" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtConversionConvertedInstrumentSharesIssued1_01a081e7-21ca-751f-ae49-45b29170b75d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtConversionConvertedInstrumentSharesIssued1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtConversionConvertedInstrumentSharesIssued1_01a081e7-21ca-751f-ae49-45b29170b75d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_PaymentsInConjunctionWithNotesExchange_01a081e7-21ca-76fa-aeb3-b4f8d154b54e" xlink:href="pacb-20260930.xsd#pacb_PaymentsInConjunctionWithNotesExchange"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_PaymentsInConjunctionWithNotesExchange_01a081e7-21ca-76fa-aeb3-b4f8d154b54e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_HoldingPeriodForTransferAssignmentOrSaleOfFounderShares_01a081e7-21ca-76e4-994c-efc4d1c23c45" xlink:href="pacb-20260930.xsd#pacb_HoldingPeriodForTransferAssignmentOrSaleOfFounderShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_HoldingPeriodForTransferAssignmentOrSaleOfFounderShares_01a081e7-21ca-76e4-994c-efc4d1c23c45" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtInstrumentCovenantMaximumAmount_01a081e7-21ca-74ae-9efa-67566503cbea" xlink:href="pacb-20260930.xsd#pacb_DebtInstrumentCovenantMaximumAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_DebtInstrumentCovenantMaximumAmount_01a081e7-21ca-74ae-9efa-67566503cbea" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger_01a081e7-21ca-7c4b-b64f-2af98266bcb0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger_01a081e7-21ca-7c4b-b64f-2af98266bcb0" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionRatio1_01a081e7-21ca-7876-a8f8-239279b1424e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentConvertibleConversionRatio1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionRatio1_01a081e7-21ca-7876-a8f8-239279b1424e" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_01a081e7-21ca-7109-8a28-03d6edb5197d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_01a081e7-21ca-7109-8a28-03d6edb5197d" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdTradingDays_01a081e7-21ca-766d-af36-06cfb120b997" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentConvertibleThresholdTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdTradingDays_01a081e7-21ca-766d-af36-06cfb120b997" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1_01a081e7-21ca-7168-9cf7-8e0ad75820c5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1_01a081e7-21ca-7168-9cf7-8e0ad75820c5" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPricePercentage_01a081e7-21ca-73a4-8115-e091a7cc4b1b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentRedemptionPricePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPricePercentage_01a081e7-21ca-73a4-8115-e091a7cc4b1b" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtInstrumentDebtDefaultCalendarDays_01a081e7-21ca-7d36-883a-19054dc1435c" xlink:href="pacb-20260930.xsd#pacb_DebtInstrumentDebtDefaultCalendarDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_DebtInstrumentDebtDefaultCalendarDays_01a081e7-21ca-7d36-883a-19054dc1435c" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtInstrumentInterestInTheEventOfDefault_01a081e7-21ca-7116-8eb8-a5b9840eb2c6" xlink:href="pacb-20260930.xsd#pacb_DebtInstrumentInterestInTheEventOfDefault"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_DebtInstrumentInterestInTheEventOfDefault_01a081e7-21ca-7116-8eb8-a5b9840eb2c6" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtInstrumentAdditionalInterestInEventOfDefault_01a081e7-21ca-747a-9972-39b78a983f41" xlink:href="pacb-20260930.xsd#pacb_DebtInstrumentAdditionalInterestInEventOfDefault"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_DebtInstrumentAdditionalInterestInEventOfDefault_01a081e7-21ca-747a-9972-39b78a983f41" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnRestructuringOfDebt_01a081e7-21ca-72e6-a0e6-9fb03146e783" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GainsLossesOnRestructuringOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_GainsLossesOnRestructuringOfDebt_01a081e7-21ca-72e6-a0e6-9fb03146e783" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringOfDebtPricePerShare_01a081e7-21ca-70fc-89bc-c6b8a100cf4f" xlink:href="pacb-20260930.xsd#pacb_RestructuringOfDebtPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_RestructuringOfDebtPricePerShare_01a081e7-21ca-70fc-89bc-c6b8a100cf4f" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFinanceCostsGross_01a081e7-21ca-7b2b-80c5-1f62a26ff6d1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DeferredFinanceCostsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DeferredFinanceCostsGross_01a081e7-21ca-7b2b-80c5-1f62a26ff6d1" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtIssuanceCostLenderFees_01a081e7-21ca-7777-aeef-60e45783d4e2" xlink:href="pacb-20260930.xsd#pacb_DebtIssuanceCostLenderFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_DebtIssuanceCostLenderFees_01a081e7-21ca-7777-aeef-60e45783d4e2" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentPeriodicPaymentInterest_01a081e7-21ca-7d16-9143-048319fc5edf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentPeriodicPaymentInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentPeriodicPaymentInterest_01a081e7-21ca-7d16-9143-048319fc5edf" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_01a081e7-21ca-7bb6-b04a-03457eb1427b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_LongTermDebt_01a081e7-21ca-7bb6-b04a-03457eb1427b" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleNotesPayable_01a081e7-21ca-78e7-bc1b-ef10a494a748" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleNotesPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_ConvertibleNotesPayable_01a081e7-21ca-78e7-bc1b-ef10a494a748" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleLongTermNotesPayable_01a081e7-21ca-7be0-9205-9a19f766cc6a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleLongTermNotesPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_ConvertibleLongTermNotesPayable_01a081e7-21ca-7be0-9205-9a19f766cc6a" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_01a081e7-21ca-7acd-8ed9-b698e597ee7c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent_01a081e7-21ca-7acd-8ed9-b698e597ee7c" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtFairValueDisclosures_01a081e7-21ca-79cc-bd75-5fe98c8d9b4a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleDebtFairValueDisclosures"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_ConvertibleDebtFairValueDisclosures_01a081e7-21ca-79cc-bd75-5fe98c8d9b4a" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtInstrumentRedemptionPricePercentageOfConversionPrice_01a081e7-21ca-76c4-b744-31598586e7c1" xlink:href="pacb-20260930.xsd#pacb_DebtInstrumentRedemptionPricePercentageOfConversionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_DebtInstrumentRedemptionPricePercentageOfConversionPrice_01a081e7-21ca-76c4-b744-31598586e7c1" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtInstrumentRedemptionPriceTradingDays_01a081e7-21ca-7730-b4c7-1fa0d2182e67" xlink:href="pacb-20260930.xsd#pacb_DebtInstrumentRedemptionPriceTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_DebtInstrumentRedemptionPriceTradingDays_01a081e7-21ca-7730-b4c7-1fa0d2182e67" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_DebtInstrumentRedemptionPriceConsecutiveTradingDays_01a081e7-21ca-7c24-bfa4-6d08d70c7e0b" xlink:href="pacb-20260930.xsd#pacb_DebtInstrumentRedemptionPriceConsecutiveTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_pacb_DebtInstrumentRedemptionPriceConsecutiveTradingDays_01a081e7-21ca-7c24-bfa4-6d08d70c7e0b" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_01a081e7-21ca-7519-93ba-f44353e48451" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7c80-88f4-105d1f52c3f9" xlink:to="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_01a081e7-21ca-7519-93ba-f44353e48451" xlink:type="arc" order="29"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/CONVERTIBLESENIORNOTESScheduleofChangestothe2029NotesDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#CONVERTIBLESENIORNOTESScheduleofChangestothe2029NotesDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/CONVERTIBLESENIORNOTESScheduleofChangestothe2029NotesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7b22-8882-5e7521e2e509" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-7d81-ae73-eeac2010d479" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7b22-8882-5e7521e2e509" xlink:to="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-7d81-ae73-eeac2010d479" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7a26-92f4-62aac792a786" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-7d81-ae73-eeac2010d479" xlink:to="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7a26-92f4-62aac792a786" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7a26-92f4-62aac792a786_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7a26-92f4-62aac792a786" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7a26-92f4-62aac792a786_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7ac2-bab9-91c6dd8c28fc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7a26-92f4-62aac792a786" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7ac2-bab9-91c6dd8c28fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2029NotesMember_01a081e7-21ca-728d-a660-26b9584a547f" xlink:href="pacb-20260930.xsd#pacb_A2029NotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7ac2-bab9-91c6dd8c28fc" xlink:to="loc_pacb_A2029NotesMember_01a081e7-21ca-728d-a660-26b9584a547f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleNotesPayable_01a081e7-21ca-7715-b466-97ad41a142f0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleNotesPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7b22-8882-5e7521e2e509" xlink:to="loc_us-gaap_ConvertibleNotesPayable_01a081e7-21ca-7715-b466-97ad41a142f0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebtExcludingAmortization_01a081e7-21ca-7785-be07-a29c1ec70448" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseDebtExcludingAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-7b22-8882-5e7521e2e509" xlink:to="loc_us-gaap_InterestExpenseDebtExcludingAmortization_01a081e7-21ca-7785-be07-a29c1ec70448" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleNotesPayable_01a081e7-21ca-73e0-9eaf-da7375322d83" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleNotesPayable"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/CONVERTIBLESENIORNOTESScheduleofNetCarryingAmountDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#CONVERTIBLESENIORNOTESScheduleofNetCarryingAmountDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/CONVERTIBLESENIORNOTESScheduleofNetCarryingAmountDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-771c-beaf-63a6c1103d19" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-76e9-a3ab-15aee0a30526" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-771c-beaf-63a6c1103d19" xlink:to="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-76e9-a3ab-15aee0a30526" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7f86-a458-79854dc8b486" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-76e9-a3ab-15aee0a30526" xlink:to="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7f86-a458-79854dc8b486" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7f86-a458-79854dc8b486_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7f86-a458-79854dc8b486" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7f86-a458-79854dc8b486_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7325-9022-3249db846be5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-7f86-a458-79854dc8b486" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7325-9022-3249db846be5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2030ConvertibleSeniorNotesMember_01a081e7-21ca-77ec-b633-59cb6421ba2f" xlink:href="pacb-20260930.xsd#pacb_A2030ConvertibleSeniorNotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-7325-9022-3249db846be5" xlink:to="loc_pacb_A2030ConvertibleSeniorNotesMember_01a081e7-21ca-77ec-b633-59cb6421ba2f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_01a081e7-21ca-7b0f-a952-43425e4d03a6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-771c-beaf-63a6c1103d19" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_01a081e7-21ca-7b0f-a952-43425e4d03a6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedPremium_01a081e7-21ca-783c-932f-d7cacc753fae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentUnamortizedPremium"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-771c-beaf-63a6c1103d19" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedPremium_01a081e7-21ca-783c-932f-d7cacc753fae" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnamortizedDebtIssuanceExpense_01a081e7-21ca-7c6e-b5bd-de586de65cd8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_UnamortizedDebtIssuanceExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-771c-beaf-63a6c1103d19" xlink:to="loc_us-gaap_UnamortizedDebtIssuanceExpense_01a081e7-21ca-7c6e-b5bd-de586de65cd8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_01a081e7-21ca-7ca5-9146-c82218cc502d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-771c-beaf-63a6c1103d19" xlink:to="loc_us-gaap_LongTermDebt_01a081e7-21ca-7ca5-9146-c82218cc502d" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/CONVERTIBLESENIORNOTESScheduleofInterestExpenseDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#CONVERTIBLESENIORNOTESScheduleofInterestExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/CONVERTIBLESENIORNOTESScheduleofInterestExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-74d4-8273-30f899c46736" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-701a-a5de-bfdf7d6a6909" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-74d4-8273-30f899c46736" xlink:to="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-701a-a5de-bfdf7d6a6909" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-78e9-b007-01889a04fc7c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_01a081e7-21ca-701a-a5de-bfdf7d6a6909" xlink:to="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-78e9-b007-01889a04fc7c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-78e9-b007-01889a04fc7c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-78e9-b007-01889a04fc7c" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-78e9-b007-01889a04fc7c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-77b1-a9b9-8da4005fa324" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a081e7-21ca-78e9-b007-01889a04fc7c" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-77b1-a9b9-8da4005fa324" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2030ConvertibleSeniorNotesMember_01a081e7-21ca-7b7b-91da-6a860bba085e" xlink:href="pacb-20260930.xsd#pacb_A2030ConvertibleSeniorNotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a081e7-21ca-77b1-a9b9-8da4005fa324" xlink:to="loc_pacb_A2030ConvertibleSeniorNotesMember_01a081e7-21ca-7b7b-91da-6a860bba085e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebtExcludingAmortization_01a081e7-21ca-76de-a7de-0ffffd048b54" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseDebtExcludingAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-74d4-8273-30f899c46736" xlink:to="loc_us-gaap_InterestExpenseDebtExcludingAmortization_01a081e7-21ca-76de-a7de-0ffffd048b54" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCosts_01a081e7-21ca-7d62-b6e7-bf34c79fbb9c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AmortizationOfFinancingCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-74d4-8273-30f899c46736" xlink:to="loc_us-gaap_AmortizationOfFinancingCosts_01a081e7-21ca-7d62-b6e7-bf34c79fbb9c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebt_01a081e7-21ca-7a3e-bd15-cf2ede574766" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a081e7-21ca-74d4-8273-30f899c46736" xlink:to="loc_us-gaap_InterestExpenseDebt_01a081e7-21ca-7a3e-bd15-cf2ede574766" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/RESTRUCTURINGNarrativeDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#RESTRUCTURINGNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/RESTRUCTURINGNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCostAndReserveLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-77d7-810a-c2629b8a3b44" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfRestructuringAndRelatedCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-77d7-810a-c2629b8a3b44" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a15e72-f4c2-7569-b37e-1698545b9d82" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-77d7-810a-c2629b8a3b44" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a15e72-f4c2-7569-b37e-1698545b9d82" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-77d9-858d-c44eab22f328" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-77d7-810a-c2629b8a3b44" xlink:to="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-77d9-858d-c44eab22f328" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-77d9-858d-c44eab22f328_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-77d9-858d-c44eab22f328" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-77d9-858d-c44eab22f328_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7b4a-987f-1d81659e8a68" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-77d9-858d-c44eab22f328" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7b4a-987f-1d81659e8a68" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2026RestructuringAndReductionForceMember_01a15dcb-f96f-7ad4-94b0-d6aa9a6dcd5c" xlink:href="pacb-20260930.xsd#pacb_A2026RestructuringAndReductionForceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7b4a-987f-1d81659e8a68" xlink:to="loc_pacb_A2026RestructuringAndReductionForceMember_01a15dcb-f96f-7ad4-94b0-d6aa9a6dcd5c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2025RestructuringMember_01a081e7-21cb-7c31-83cf-4428b3c60c04" xlink:href="pacb-20260930.xsd#pacb_A2025RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7b4a-987f-1d81659e8a68" xlink:to="loc_pacb_A2025RestructuringMember_01a081e7-21cb-7c31-83cf-4428b3c60c04" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2024RestructuringMember_01a081e7-21cb-708d-be98-e02dab32b073" xlink:href="pacb-20260930.xsd#pacb_A2024RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7b4a-987f-1d81659e8a68" xlink:to="loc_pacb_A2024RestructuringMember_01a081e7-21cb-708d-be98-e02dab32b073" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21cb-79ac-8c59-2e77c55e090b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-77d7-810a-c2629b8a3b44" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21cb-79ac-8c59-2e77c55e090b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21cb-79ac-8c59-2e77c55e090b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21cb-79ac-8c59-2e77c55e090b" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21cb-79ac-8c59-2e77c55e090b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21cb-7792-9369-62a63442a2c5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21cb-79ac-8c59-2e77c55e090b" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21cb-7792-9369-62a63442a2c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_InProcessResearchAndDevelopmentIndefiniteLivedMember_01a081e7-21cb-759f-b17b-15754e694382" xlink:href="pacb-20260930.xsd#pacb_InProcessResearchAndDevelopmentIndefiniteLivedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21cb-7792-9369-62a63442a2c5" xlink:to="loc_pacb_InProcessResearchAndDevelopmentIndefiniteLivedMember_01a081e7-21cb-759f-b17b-15754e694382" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminated_01a139da-241b-72fb-8a4d-9472f8034df0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminated"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminated_01a139da-241b-72fb-8a4d-9472f8034df0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminatedPeriodPercent_01a139da-241b-747c-a664-dbd2158c9d01" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminatedPeriodPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminatedPeriodPercent_01a139da-241b-747c-a664-dbd2158c9d01" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCharges_01a081e7-21cb-7399-a68b-aa368ba58572" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCharges"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_RestructuringCharges_01a081e7-21cb-7399-a68b-aa368ba58572" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringChargesWorkerAdjustmentAndRetrainingNotificationWARNActAndOtherEmployeeBenefits_01a081e7-21cb-754c-b677-783f1d8b7da3" xlink:href="pacb-20260930.xsd#pacb_RestructuringChargesWorkerAdjustmentAndRetrainingNotificationWARNActAndOtherEmployeeBenefits"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_pacb_RestructuringChargesWorkerAdjustmentAndRetrainingNotificationWARNActAndOtherEmployeeBenefits_01a081e7-21cb-754c-b677-783f1d8b7da3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeveranceCosts1_01a081e7-21cb-76f6-868f-55fcecc5e5a1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeveranceCosts1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_SeveranceCosts1_01a081e7-21cb-76f6-868f-55fcecc5e5a1" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringChargesAdditionalCostsIncurred_01a081e7-21cb-7d96-8b65-8417faa7f0fe" xlink:href="pacb-20260930.xsd#pacb_RestructuringChargesAdditionalCostsIncurred"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_pacb_RestructuringChargesAdditionalCostsIncurred_01a081e7-21cb-7d96-8b65-8417faa7f0fe" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21cb-7a25-ae35-9101652cc8dc" xlink:href="pacb-20260930.xsd#pacb_RestructuringAndRelatedCostAcceleratedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21cb-7a25-ae35-9101652cc8dc" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill_01a081e7-21cb-7a5b-a6be-9e9c0d79c4ed" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill_01a081e7-21cb-7a5b-a6be-9e9c0d79c4ed" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWriteDown_01a081e7-21cb-7a0b-a031-f1f8baaeb9b6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InventoryWriteDown"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_InventoryWriteDown_01a081e7-21cb-7a0b-a031-f1f8baaeb9b6" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_GainLossOnPurchaseCommitments_01a081e7-21cb-7b13-b7e5-fdf0edbbcebe" xlink:href="pacb-20260930.xsd#pacb_GainLossOnPurchaseCommitments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_pacb_GainLossOnPurchaseCommitments_01a081e7-21cb-7b13-b7e5-fdf0edbbcebe" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringReserveAcceleratedDepreciation_01a081e7-21cb-7e29-87ea-b6d58a5f7388" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringReserveAcceleratedDepreciation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_RestructuringReserveAcceleratedDepreciation_01a081e7-21cb-7e29-87ea-b6d58a5f7388" xlink:type="arc" order="10"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/RESTRUCTURINGNarrativeDetails_1" xlink:type="simple" xlink:href="pacb-20260930.xsd#RESTRUCTURINGNarrativeDetails_1"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/RESTRUCTURINGNarrativeDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCostAndReserveLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-77d7-810a-c2629b8a3b44" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfRestructuringAndRelatedCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-77d7-810a-c2629b8a3b44" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-77d9-858d-c44eab22f328" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-77d7-810a-c2629b8a3b44" xlink:to="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-77d9-858d-c44eab22f328" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-77d9-858d-c44eab22f328_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-77d9-858d-c44eab22f328" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-77d9-858d-c44eab22f328_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7b4a-987f-1d81659e8a68" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-77d9-858d-c44eab22f328" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7b4a-987f-1d81659e8a68" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2026RestructuringAndReductionForceMember_01a15dcb-f96f-7ad4-94b0-d6aa9a6dcd5c" xlink:href="pacb-20260930.xsd#pacb_A2026RestructuringAndReductionForceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7b4a-987f-1d81659e8a68" xlink:to="loc_pacb_A2026RestructuringAndReductionForceMember_01a15dcb-f96f-7ad4-94b0-d6aa9a6dcd5c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2025RestructuringMember_01a081e7-21cb-7c31-83cf-4428b3c60c04" xlink:href="pacb-20260930.xsd#pacb_A2025RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7b4a-987f-1d81659e8a68" xlink:to="loc_pacb_A2025RestructuringMember_01a081e7-21cb-7c31-83cf-4428b3c60c04" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2024RestructuringMember_01a081e7-21cb-708d-be98-e02dab32b073" xlink:href="pacb-20260930.xsd#pacb_A2024RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7b4a-987f-1d81659e8a68" xlink:to="loc_pacb_A2024RestructuringMember_01a081e7-21cb-708d-be98-e02dab32b073" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21cb-79ac-8c59-2e77c55e090b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-77d7-810a-c2629b8a3b44" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21cb-79ac-8c59-2e77c55e090b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21cb-79ac-8c59-2e77c55e090b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21cb-79ac-8c59-2e77c55e090b" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21cb-79ac-8c59-2e77c55e090b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21cb-7792-9369-62a63442a2c5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis_01a081e7-21cb-79ac-8c59-2e77c55e090b" xlink:to="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21cb-7792-9369-62a63442a2c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_InProcessResearchAndDevelopmentIndefiniteLivedMember_01a081e7-21cb-759f-b17b-15754e694382" xlink:href="pacb-20260930.xsd#pacb_InProcessResearchAndDevelopmentIndefiniteLivedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_01a081e7-21cb-7792-9369-62a63442a2c5" xlink:to="loc_pacb_InProcessResearchAndDevelopmentIndefiniteLivedMember_01a081e7-21cb-759f-b17b-15754e694382" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminated_01a139da-241b-72fb-8a4d-9472f8034df0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminated"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminated_01a139da-241b-72fb-8a4d-9472f8034df0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminatedPeriodPercent_01a139da-241b-747c-a664-dbd2158c9d01" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminatedPeriodPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_RestructuringAndRelatedCostNumberOfPositionsEliminatedPeriodPercent_01a139da-241b-747c-a664-dbd2158c9d01" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCharges_01a081e7-21cb-7399-a68b-aa368ba58572" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCharges"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_RestructuringCharges_01a081e7-21cb-7399-a68b-aa368ba58572" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringChargesWorkerAdjustmentAndRetrainingNotificationWARNActAndOtherEmployeeBenefits_01a081e7-21cb-754c-b677-783f1d8b7da3" xlink:href="pacb-20260930.xsd#pacb_RestructuringChargesWorkerAdjustmentAndRetrainingNotificationWARNActAndOtherEmployeeBenefits"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_pacb_RestructuringChargesWorkerAdjustmentAndRetrainingNotificationWARNActAndOtherEmployeeBenefits_01a081e7-21cb-754c-b677-783f1d8b7da3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeveranceCosts1_01a081e7-21cb-76f6-868f-55fcecc5e5a1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeveranceCosts1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_SeveranceCosts1_01a081e7-21cb-76f6-868f-55fcecc5e5a1" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringChargesAdditionalCostsIncurred_01a081e7-21cb-7d96-8b65-8417faa7f0fe" xlink:href="pacb-20260930.xsd#pacb_RestructuringChargesAdditionalCostsIncurred"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_pacb_RestructuringChargesAdditionalCostsIncurred_01a081e7-21cb-7d96-8b65-8417faa7f0fe" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21cb-7a25-ae35-9101652cc8dc" xlink:href="pacb-20260930.xsd#pacb_RestructuringAndRelatedCostAcceleratedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_pacb_RestructuringAndRelatedCostAcceleratedAmortization_01a081e7-21cb-7a25-ae35-9101652cc8dc" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill_01a081e7-21cb-7a5b-a6be-9e9c0d79c4ed" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill_01a081e7-21cb-7a5b-a6be-9e9c0d79c4ed" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWriteDown_01a081e7-21cb-7a0b-a031-f1f8baaeb9b6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InventoryWriteDown"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_InventoryWriteDown_01a081e7-21cb-7a0b-a031-f1f8baaeb9b6" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_GainLossOnPurchaseCommitments_01a081e7-21cb-7b13-b7e5-fdf0edbbcebe" xlink:href="pacb-20260930.xsd#pacb_GainLossOnPurchaseCommitments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_pacb_GainLossOnPurchaseCommitments_01a081e7-21cb-7b13-b7e5-fdf0edbbcebe" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringReserveAcceleratedDepreciation_01a081e7-21cb-7e29-87ea-b6d58a5f7388" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringReserveAcceleratedDepreciation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7c8e-8600-401c75ee5082" xlink:to="loc_us-gaap_RestructuringReserveAcceleratedDepreciation_01a081e7-21cb-7e29-87ea-b6d58a5f7388" xlink:type="arc" order="10"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/RESTRUCTURINGScheduleofPreTaxRestructuringChargesDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#RESTRUCTURINGScheduleofPreTaxRestructuringChargesDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/RESTRUCTURINGScheduleofPreTaxRestructuringChargesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7843-879d-fa631a9a41e2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCostAndReserveLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-7f6a-8fe0-5963c19dfe52" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfRestructuringAndRelatedCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7843-879d-fa631a9a41e2" xlink:to="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-7f6a-8fe0-5963c19dfe52" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCostAndReserveAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-7f6a-8fe0-5963c19dfe52" xlink:to="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TypeOfRestructuringDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac" xlink:to="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-7472-b90f-c48092464b98" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TypeOfRestructuringDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac" xlink:to="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-7472-b90f-c48092464b98" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_EmployeeSeparationCostsMember_01a081e7-21cb-7168-8be2-3bf5c468f3ca" xlink:href="pacb-20260930.xsd#pacb_EmployeeSeparationCostsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-7472-b90f-c48092464b98" xlink:to="loc_pacb_EmployeeSeparationCostsMember_01a081e7-21cb-7168-8be2-3bf5c468f3ca" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherRestructuringMember_01a081e7-21cb-7d75-be0f-8b47908b36bf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherRestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-7472-b90f-c48092464b98" xlink:to="loc_us-gaap_OtherRestructuringMember_01a081e7-21cb-7d75-be0f-8b47908b36bf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a081e7-21cb-7d88-b960-45016c37dc51" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-7f6a-8fe0-5963c19dfe52" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a081e7-21cb-7d88-b960-45016c37dc51" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-71c4-9b32-b37e3304a87c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-7f6a-8fe0-5963c19dfe52" xlink:to="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-71c4-9b32-b37e3304a87c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-71c4-9b32-b37e3304a87c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-71c4-9b32-b37e3304a87c" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-71c4-9b32-b37e3304a87c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-75ad-ac3d-7424215952d9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-71c4-9b32-b37e3304a87c" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-75ad-ac3d-7424215952d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2025RestructuringMember_01a081e7-21cb-7bb0-834a-884a78d99def" xlink:href="pacb-20260930.xsd#pacb_A2025RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-75ad-ac3d-7424215952d9" xlink:to="loc_pacb_A2025RestructuringMember_01a081e7-21cb-7bb0-834a-884a78d99def" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringAndRelatedCostIncurredCost_01a081e7-21cb-70b0-a33a-fb57abc83670" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringAndRelatedCostIncurredCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7843-879d-fa631a9a41e2" xlink:to="loc_us-gaap_RestructuringAndRelatedCostIncurredCost_01a081e7-21cb-70b0-a33a-fb57abc83670" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/RESTRUCTURINGScheduleofPreTaxRestructuringChargesDetails_1" xlink:type="simple" xlink:href="pacb-20260930.xsd#RESTRUCTURINGScheduleofPreTaxRestructuringChargesDetails_1"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/RESTRUCTURINGScheduleofPreTaxRestructuringChargesDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7843-879d-fa631a9a41e2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCostAndReserveLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-7f6a-8fe0-5963c19dfe52" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfRestructuringAndRelatedCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7843-879d-fa631a9a41e2" xlink:to="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-7f6a-8fe0-5963c19dfe52" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCostAndReserveAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-7f6a-8fe0-5963c19dfe52" xlink:to="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TypeOfRestructuringDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac" xlink:to="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-7472-b90f-c48092464b98" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TypeOfRestructuringDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-70ee-a4dc-a9ef2d1d13ac" xlink:to="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-7472-b90f-c48092464b98" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_EmployeeSeparationCostsMember_01a081e7-21cb-7168-8be2-3bf5c468f3ca" xlink:href="pacb-20260930.xsd#pacb_EmployeeSeparationCostsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-7472-b90f-c48092464b98" xlink:to="loc_pacb_EmployeeSeparationCostsMember_01a081e7-21cb-7168-8be2-3bf5c468f3ca" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherRestructuringMember_01a081e7-21cb-7d75-be0f-8b47908b36bf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherRestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-7472-b90f-c48092464b98" xlink:to="loc_us-gaap_OtherRestructuringMember_01a081e7-21cb-7d75-be0f-8b47908b36bf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-71c4-9b32-b37e3304a87c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-7f6a-8fe0-5963c19dfe52" xlink:to="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-71c4-9b32-b37e3304a87c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-71c4-9b32-b37e3304a87c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-71c4-9b32-b37e3304a87c" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-71c4-9b32-b37e3304a87c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-75ad-ac3d-7424215952d9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-71c4-9b32-b37e3304a87c" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-75ad-ac3d-7424215952d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2025RestructuringMember_01a081e7-21cb-7bb0-834a-884a78d99def" xlink:href="pacb-20260930.xsd#pacb_A2025RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-75ad-ac3d-7424215952d9" xlink:to="loc_pacb_A2025RestructuringMember_01a081e7-21cb-7bb0-834a-884a78d99def" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringAndRelatedCostIncurredCost_01a081e7-21cb-70b0-a33a-fb57abc83670" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringAndRelatedCostIncurredCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-7843-879d-fa631a9a41e2" xlink:to="loc_us-gaap_RestructuringAndRelatedCostIncurredCost_01a081e7-21cb-70b0-a33a-fb57abc83670" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/RESTRUCTURINGScheduleofLiabilitiesRelatedtoRestructuringDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#RESTRUCTURINGScheduleofLiabilitiesRelatedtoRestructuringDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/RESTRUCTURINGScheduleofLiabilitiesRelatedtoRestructuringDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-79da-a15d-19104bb63e6f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCostAndReserveLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-75d1-89e0-3f15d72a05df" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfRestructuringAndRelatedCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-79da-a15d-19104bb63e6f" xlink:to="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-75d1-89e0-3f15d72a05df" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-75ca-82af-cbe05a7daa9c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCostAndReserveAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-75d1-89e0-3f15d72a05df" xlink:to="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-75ca-82af-cbe05a7daa9c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-75ca-82af-cbe05a7daa9c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TypeOfRestructuringDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-75ca-82af-cbe05a7daa9c" xlink:to="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-75ca-82af-cbe05a7daa9c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-755f-81a4-f93ac5295a18" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TypeOfRestructuringDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringCostAndReserveAxis_01a081e7-21cb-75ca-82af-cbe05a7daa9c" xlink:to="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-755f-81a4-f93ac5295a18" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherRestructuringMember_01a081e7-21cb-73ef-861b-0dbf64604a19" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherRestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TypeOfRestructuringDomain_01a081e7-21cb-755f-81a4-f93ac5295a18" xlink:to="loc_us-gaap_OtherRestructuringMember_01a081e7-21cb-73ef-861b-0dbf64604a19" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-737c-966d-91c7158f0fdd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_01a081e7-21cb-75d1-89e0-3f15d72a05df" xlink:to="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-737c-966d-91c7158f0fdd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-737c-966d-91c7158f0fdd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-737c-966d-91c7158f0fdd" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-737c-966d-91c7158f0fdd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7f3a-bccc-0f5ab42b56b2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringPlanDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringPlanAxis_01a081e7-21cb-737c-966d-91c7158f0fdd" xlink:to="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7f3a-bccc-0f5ab42b56b2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2025RestructuringMember_01a081e7-21cb-777a-8dd6-624774324647" xlink:href="pacb-20260930.xsd#pacb_A2025RestructuringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringPlanDomain_01a081e7-21cb-7f3a-bccc-0f5ab42b56b2" xlink:to="loc_pacb_A2025RestructuringMember_01a081e7-21cb-777a-8dd6-624774324647" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringReserve_01a081e7-21cb-76ca-b4df-cd05b519cba7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringReserve"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-79da-a15d-19104bb63e6f" xlink:to="loc_us-gaap_RestructuringReserve_01a081e7-21cb-76ca-b4df-cd05b519cba7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRestructuring_01a081e7-21cb-7a0f-be59-44eefe9c756d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsForRestructuring"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-79da-a15d-19104bb63e6f" xlink:to="loc_us-gaap_PaymentsForRestructuring_01a081e7-21cb-7a0f-be59-44eefe9c756d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringReserve_01a081e7-21cb-72f2-ad1e-bad5975ad849" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringReserve"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_01a081e7-21cb-723a-9236-0b969904ab49" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_01a081e7-21cb-79da-a15d-19104bb63e6f" xlink:to="loc_us-gaap_RestructuringAndRelatedCostExpectedCostRemaining1_01a081e7-21cb-723a-9236-0b969904ab49" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONNarrativeDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#EQUITYPLANSANDSHAREBASEDCOMPENSATIONNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-704c-b5d8-a7f376ec3903" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7b3f-b477-3421d74ee3ac" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-704c-b5d8-a7f376ec3903" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7b3f-b477-3421d74ee3ac" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredCompensationArrangementWithIndividualShareBasedPaymentsByTypeOfDeferredCompensationAxis_01a081e7-21cb-753b-8999-47eb1baa6f60" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DeferredCompensationArrangementWithIndividualShareBasedPaymentsByTypeOfDeferredCompensationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7b3f-b477-3421d74ee3ac" xlink:to="loc_us-gaap_DeferredCompensationArrangementWithIndividualShareBasedPaymentsByTypeOfDeferredCompensationAxis_01a081e7-21cb-753b-8999-47eb1baa6f60" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityBasedArrangementsIndividualContractsTypeOfDeferredCompensationDomain_01a081e7-21cb-753b-8999-47eb1baa6f60_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityBasedArrangementsIndividualContractsTypeOfDeferredCompensationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DeferredCompensationArrangementWithIndividualShareBasedPaymentsByTypeOfDeferredCompensationAxis_01a081e7-21cb-753b-8999-47eb1baa6f60" xlink:to="loc_us-gaap_EquityBasedArrangementsIndividualContractsTypeOfDeferredCompensationDomain_01a081e7-21cb-753b-8999-47eb1baa6f60_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityBasedArrangementsIndividualContractsTypeOfDeferredCompensationDomain_01a081e7-21cb-7825-a08d-26bf42b2b2f4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityBasedArrangementsIndividualContractsTypeOfDeferredCompensationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DeferredCompensationArrangementWithIndividualShareBasedPaymentsByTypeOfDeferredCompensationAxis_01a081e7-21cb-753b-8999-47eb1baa6f60" xlink:to="loc_us-gaap_EquityBasedArrangementsIndividualContractsTypeOfDeferredCompensationDomain_01a081e7-21cb-7825-a08d-26bf42b2b2f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_EquityIncentivePlan2020Member_01a081e7-21cb-7b31-bb20-7a71cc7116b0" xlink:href="pacb-20260930.xsd#pacb_EquityIncentivePlan2020Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityBasedArrangementsIndividualContractsTypeOfDeferredCompensationDomain_01a081e7-21cb-7825-a08d-26bf42b2b2f4" xlink:to="loc_pacb_EquityIncentivePlan2020Member_01a081e7-21cb-7b31-bb20-7a71cc7116b0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_EmployeeStockPurchasePlanMember_01a081e7-21cb-78d8-8a8c-e54cec742f76" xlink:href="pacb-20260930.xsd#pacb_EmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityBasedArrangementsIndividualContractsTypeOfDeferredCompensationDomain_01a081e7-21cb-7825-a08d-26bf42b2b2f4" xlink:to="loc_pacb_EmployeeStockPurchasePlanMember_01a081e7-21cb-78d8-8a8c-e54cec742f76" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_01a081e7-21cb-7203-9496-8a73efdfb48d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7b3f-b477-3421d74ee3ac" xlink:to="loc_us-gaap_PlanNameAxis_01a081e7-21cb-7203-9496-8a73efdfb48d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_01a081e7-21cb-7203-9496-8a73efdfb48d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_01a081e7-21cb-7203-9496-8a73efdfb48d" xlink:to="loc_us-gaap_PlanNameDomain_01a081e7-21cb-7203-9496-8a73efdfb48d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_01a081e7-21cb-76cd-bf9e-0b5998f12330" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_01a081e7-21cb-7203-9496-8a73efdfb48d" xlink:to="loc_us-gaap_PlanNameDomain_01a081e7-21cb-76cd-bf9e-0b5998f12330" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_A2020PlanInducementPlanAndTheOmniomePlanMember_01a081e7-21cb-7caa-af22-29b6b117a9ed" xlink:href="pacb-20260930.xsd#pacb_A2020PlanInducementPlanAndTheOmniomePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_01a081e7-21cb-76cd-bf9e-0b5998f12330" xlink:to="loc_pacb_A2020PlanInducementPlanAndTheOmniomePlanMember_01a081e7-21cb-7caa-af22-29b6b117a9ed" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7fae-8feb-967108a7a0b9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7b3f-b477-3421d74ee3ac" xlink:to="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7fae-8feb-967108a7a0b9" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7fae-8feb-967108a7a0b9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7fae-8feb-967108a7a0b9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7fae-8feb-967108a7a0b9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7747-a387-e84a1f8bc3de" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7fae-8feb-967108a7a0b9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7747-a387-e84a1f8bc3de" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_TimeBasedRestrictedStockUnitsPSUMember_01a081e7-21cb-7b39-b685-2001e6f78bf0" xlink:href="pacb-20260930.xsd#pacb_TimeBasedRestrictedStockUnitsPSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7747-a387-e84a1f8bc3de" xlink:to="loc_pacb_TimeBasedRestrictedStockUnitsPSUMember_01a081e7-21cb-7b39-b685-2001e6f78bf0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_01a081e7-21cb-7076-a66c-dcb50c622c44" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-704c-b5d8-a7f376ec3903" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_01a081e7-21cb-7076-a66c-dcb50c622c44" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_01a081e7-21cb-7aca-aab6-f8301e66daea" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-704c-b5d8-a7f376ec3903" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_01a081e7-21cb-7aca-aab6-f8301e66daea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ShareBasedCompensationArrangementByShareBasedPaymentAwardAmountEligibleToVestUponAchievementOfGoal_01a081e7-21cb-7cc2-850e-9fa9182cb467" xlink:href="pacb-20260930.xsd#pacb_ShareBasedCompensationArrangementByShareBasedPaymentAwardAmountEligibleToVestUponAchievementOfGoal"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-704c-b5d8-a7f376ec3903" xlink:to="loc_pacb_ShareBasedCompensationArrangementByShareBasedPaymentAwardAmountEligibleToVestUponAchievementOfGoal_01a081e7-21cb-7cc2-850e-9fa9182cb467" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockOwnershipPlan_01a081e7-21cb-785f-b33e-31d10222819d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockOwnershipPlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-704c-b5d8-a7f376ec3903" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockOwnershipPlan_01a081e7-21cb-785f-b33e-31d10222819d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_01a081e7-21cb-71c2-8ea8-a2c2feec3565" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-704c-b5d8-a7f376ec3903" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_01a081e7-21cb-71c2-8ea8-a2c2feec3565" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_01a081e7-21cb-768e-a859-4f951b624d0d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-704c-b5d8-a7f376ec3903" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_01a081e7-21cb-768e-a859-4f951b624d0d" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofStockOptionActivityDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofStockOptionActivityDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofStockOptionActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-741a-9bdf-3a8b13dc99f8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7e40-909f-6ce5eadade24" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-741a-9bdf-3a8b13dc99f8" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7e40-909f-6ce5eadade24" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7a51-b218-b9d68e517e25" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7e40-909f-6ce5eadade24" xlink:to="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7a51-b218-b9d68e517e25" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7a51-b218-b9d68e517e25_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7a51-b218-b9d68e517e25" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7a51-b218-b9d68e517e25_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-73e2-9cf4-38aeeb44a542" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7a51-b218-b9d68e517e25" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-73e2-9cf4-38aeeb44a542" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_TimeBasedStockOptionMember_01a081e7-21cb-77c1-92be-f8be2a3ef2a0" xlink:href="pacb-20260930.xsd#pacb_TimeBasedStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-73e2-9cf4-38aeeb44a542" xlink:to="loc_pacb_TimeBasedStockOptionMember_01a081e7-21cb-77c1-92be-f8be2a3ef2a0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7b92-89e5-f56cdaf619ff" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-741a-9bdf-3a8b13dc99f8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7b92-89e5-f56cdaf619ff" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_01a081e7-21cb-7677-a024-27bf2761f751" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7b92-89e5-f56cdaf619ff" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_01a081e7-21cb-7677-a024-27bf2761f751" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_01a081e7-21cb-7050-97f0-a1d8b11ab36a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7b92-89e5-f56cdaf619ff" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_01a081e7-21cb-7050-97f0-a1d8b11ab36a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_01a081e7-21cb-7577-a521-a94009d988e3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7b92-89e5-f56cdaf619ff" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_01a081e7-21cb-7577-a521-a94009d988e3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_01a081e7-21cb-74b7-8a8f-472594b8c395" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7b92-89e5-f56cdaf619ff" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_01a081e7-21cb-74b7-8a8f-472594b8c395" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_01a081e7-21cb-73eb-bb51-04cdbc67528e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7977-a582-cff64d73286e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-741a-9bdf-3a8b13dc99f8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7977-a582-cff64d73286e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_01a081e7-21cb-7300-ae6b-85bb493dfb79" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7977-a582-cff64d73286e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_01a081e7-21cb-7300-ae6b-85bb493dfb79" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_01a081e7-21cb-7ecc-bdf5-7e9dbe8d5fbc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7977-a582-cff64d73286e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_01a081e7-21cb-7ecc-bdf5-7e9dbe8d5fbc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_01a081e7-21cb-7461-bf73-fe446e3dbe34" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7977-a582-cff64d73286e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_01a081e7-21cb-7461-bf73-fe446e3dbe34" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice_01a081e7-21cb-762b-8b2b-fd4f1c61745e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7977-a582-cff64d73286e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice_01a081e7-21cb-762b-8b2b-fd4f1c61745e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_01a081e7-21cb-778e-b632-0b17dba092c9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofTimeBasedRSUsandPSUsActivityDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofTimeBasedRSUsandPSUsActivityDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofTimeBasedRSUsandPSUsActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-71b6-911d-466664cea1ef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7287-ba0a-cbd3409f9dce" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-71b6-911d-466664cea1ef" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7287-ba0a-cbd3409f9dce" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7fd4-b4ed-26c9732a9c1a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-7287-ba0a-cbd3409f9dce" xlink:to="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7fd4-b4ed-26c9732a9c1a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7fd4-b4ed-26c9732a9c1a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7fd4-b4ed-26c9732a9c1a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7fd4-b4ed-26c9732a9c1a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-72b3-a56b-23fd70e7ded0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7fd4-b4ed-26c9732a9c1a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-72b3-a56b-23fd70e7ded0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_TimeBasedRestrictedStockUnitsRsusMember_01a081e7-21cb-740a-8c3a-6de360a3e79a" xlink:href="pacb-20260930.xsd#pacb_TimeBasedRestrictedStockUnitsRsusMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-72b3-a56b-23fd70e7ded0" xlink:to="loc_pacb_TimeBasedRestrictedStockUnitsRsusMember_01a081e7-21cb-740a-8c3a-6de360a3e79a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_01a081e7-21cb-73ed-8caa-1c30973f8c98" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-72b3-a56b-23fd70e7ded0" xlink:to="loc_us-gaap_PerformanceSharesMember_01a081e7-21cb-73ed-8caa-1c30973f8c98" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7dee-bcac-cbc912d7d814" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-71b6-911d-466664cea1ef" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7dee-bcac-cbc912d7d814" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_01a081e7-21cb-71bf-8e7c-e7d60d478df9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7dee-bcac-cbc912d7d814" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_01a081e7-21cb-71bf-8e7c-e7d60d478df9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_01a081e7-21cb-7092-a06b-911b11c45673" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7dee-bcac-cbc912d7d814" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_01a081e7-21cb-7092-a06b-911b11c45673" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_01a081e7-21cb-7e90-a84a-49814b9961ae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7dee-bcac-cbc912d7d814" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_01a081e7-21cb-7e90-a84a-49814b9961ae" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_01a081e7-21cb-76d3-8e90-371f4fe3d388" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingRollForward_01a081e7-21cb-7dee-bcac-cbc912d7d814" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_01a081e7-21cb-76d3-8e90-371f4fe3d388" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_01a081e7-21cb-7eb3-8fbc-439962d90fe8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7248-8f1e-7af356e0f1f4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-71b6-911d-466664cea1ef" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7248-8f1e-7af356e0f1f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_01a081e7-21cb-7c03-9cb0-1f04ead451bd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7248-8f1e-7af356e0f1f4" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_01a081e7-21cb-7c03-9cb0-1f04ead451bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_01a081e7-21cb-79ec-a7c2-5c4f413e78e3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7248-8f1e-7af356e0f1f4" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_01a081e7-21cb-79ec-a7c2-5c4f413e78e3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_01a081e7-21cb-794d-aa99-c2e83813a760" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7248-8f1e-7af356e0f1f4" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_01a081e7-21cb-794d-aa99-c2e83813a760" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_01a081e7-21cb-7eeb-8329-6bfe1a0fa7ca" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a081e7-21cb-7248-8f1e-7af356e0f1f4" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_01a081e7-21cb-7eeb-8329-6bfe1a0fa7ca" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_01a081e7-21cb-7b51-add2-849213e67297" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofStockBasedCompensationExpenseDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofStockBasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofStockBasedCompensationExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_01a081e7-21cb-7174-b6a8-213462d1e1b9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_01a081e7-21cb-7142-93b0-95a6c3b189c5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_01a081e7-21cb-7174-b6a8-213462d1e1b9" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_01a081e7-21cb-7142-93b0-95a6c3b189c5" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a081e7-21cb-7ff6-a0b1-4224fb2756d5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_01a081e7-21cb-7142-93b0-95a6c3b189c5" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a081e7-21cb-7ff6-a0b1-4224fb2756d5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_01a081e7-21cb-7633-87e8-aff4d1170f27" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_01a081e7-21cb-7174-b6a8-213462d1e1b9" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_01a081e7-21cb-7633-87e8-aff4d1170f27" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofStockBasedCompensationExpenseDetails_1" xlink:type="simple" xlink:href="pacb-20260930.xsd#EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofStockBasedCompensationExpenseDetails_1"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofStockBasedCompensationExpenseDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_01a081e7-21cb-7174-b6a8-213462d1e1b9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_01a081e7-21cb-7142-93b0-95a6c3b189c5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_01a081e7-21cb-7174-b6a8-213462d1e1b9" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_01a081e7-21cb-7142-93b0-95a6c3b189c5" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_01a081e7-21cb-7633-87e8-aff4d1170f27" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_01a081e7-21cb-7174-b6a8-213462d1e1b9" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_01a081e7-21cb-7633-87e8-aff4d1170f27" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofFairValueofEmployeeStockOptionsDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofFairValueofEmployeeStockOptionsDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofFairValueofEmployeeStockOptionsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-7992-990e-263b337af1cb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-771d-bafa-4db9d47aa292" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-7992-990e-263b337af1cb" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-771d-bafa-4db9d47aa292" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7287-96f4-496d53d9c162" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-771d-bafa-4db9d47aa292" xlink:to="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7287-96f4-496d53d9c162" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7287-96f4-496d53d9c162_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7287-96f4-496d53d9c162" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-7287-96f4-496d53d9c162_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-715a-839a-931aba638322" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_01a081e7-21cb-7287-96f4-496d53d9c162" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-715a-839a-931aba638322" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_OptionsToPurchaseCommonStockMember_01a081e7-21cb-717b-9b53-93fb2408eb1f" xlink:href="pacb-20260930.xsd#pacb_OptionsToPurchaseCommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a081e7-21cb-715a-839a-931aba638322" xlink:to="loc_pacb_OptionsToPurchaseCommonStockMember_01a081e7-21cb-717b-9b53-93fb2408eb1f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_01a081e7-21cb-7a81-b7c0-72db9ff995e4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-7992-990e-263b337af1cb" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_01a081e7-21cb-7a81-b7c0-72db9ff995e4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_01a081e7-21cb-77f1-b230-3bd15104050c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-7992-990e-263b337af1cb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_01a081e7-21cb-77f1-b230-3bd15104050c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_01a081e7-21cb-76d0-9b28-ae138fce3d5f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-7992-990e-263b337af1cb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_01a081e7-21cb-76d0-9b28-ae138fce3d5f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_01a081e7-21cb-7e35-b14f-be71350a73bf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-7992-990e-263b337af1cb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_01a081e7-21cb-7e35-b14f-be71350a73bf" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_01a081e7-21cb-7ead-b979-76c7d2e1a334" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-7992-990e-263b337af1cb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_01a081e7-21cb-7ead-b979-76c7d2e1a334" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_01a081e7-21cb-7dd1-be81-eed865d1adbe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-7992-990e-263b337af1cb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_01a081e7-21cb-7dd1-be81-eed865d1adbe" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_01a081e7-21cb-7858-9b14-aa9cdcac6cab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-7992-990e-263b337af1cb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_01a081e7-21cb-7858-9b14-aa9cdcac6cab" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofFairValueofEmployeeStockPurchasePlanDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofFairValueofEmployeeStockPurchasePlanDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/EQUITYPLANSANDSHAREBASEDCOMPENSATIONScheduleofFairValueofEmployeeStockPurchasePlanDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-75b2-83c8-d9754d273056" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-72fc-a8ad-44179e1ff6ec" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-75b2-83c8-d9754d273056" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-72fc-a8ad-44179e1ff6ec" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a081e7-21cb-7c12-9a40-04ae5b7d6e68" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-72fc-a8ad-44179e1ff6ec" xlink:to="loc_srt_RangeAxis_01a081e7-21cb-7c12-9a40-04ae5b7d6e68" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a081e7-21cb-7c12-9a40-04ae5b7d6e68_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a081e7-21cb-7c12-9a40-04ae5b7d6e68" xlink:to="loc_srt_RangeMember_01a081e7-21cb-7c12-9a40-04ae5b7d6e68_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a081e7-21cb-7255-82d0-224f7c7749b4" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a081e7-21cb-7c12-9a40-04ae5b7d6e68" xlink:to="loc_srt_RangeMember_01a081e7-21cb-7255-82d0-224f7c7749b4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_01a081e7-21cb-7d51-a5cd-453dd5b31603" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a081e7-21cb-7255-82d0-224f7c7749b4" xlink:to="loc_srt_MinimumMember_01a081e7-21cb-7d51-a5cd-453dd5b31603" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_01a081e7-21cb-738e-a04d-ff220472ad7c" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a081e7-21cb-7255-82d0-224f7c7749b4" xlink:to="loc_srt_MaximumMember_01a081e7-21cb-738e-a04d-ff220472ad7c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_01a081e7-21cb-7445-ab52-0d2ccc1d9a3e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_01a081e7-21cb-72fc-a8ad-44179e1ff6ec" xlink:to="loc_us-gaap_PlanNameAxis_01a081e7-21cb-7445-ab52-0d2ccc1d9a3e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_01a081e7-21cb-7445-ab52-0d2ccc1d9a3e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_01a081e7-21cb-7445-ab52-0d2ccc1d9a3e" xlink:to="loc_us-gaap_PlanNameDomain_01a081e7-21cb-7445-ab52-0d2ccc1d9a3e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_01a081e7-21cb-7de5-97f2-c0e488f1d289" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_01a081e7-21cb-7445-ab52-0d2ccc1d9a3e" xlink:to="loc_us-gaap_PlanNameDomain_01a081e7-21cb-7de5-97f2-c0e488f1d289" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_EmployeeStockPurchasePlanMember_01a081e7-21cb-705c-a673-216bedb0e77c" xlink:href="pacb-20260930.xsd#pacb_EmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_01a081e7-21cb-7de5-97f2-c0e488f1d289" xlink:to="loc_pacb_EmployeeStockPurchasePlanMember_01a081e7-21cb-705c-a673-216bedb0e77c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_01a081e7-21cb-7179-9e8c-8b0f7e78f2d0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-75b2-83c8-d9754d273056" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_01a081e7-21cb-7179-9e8c-8b0f7e78f2d0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_01a139dd-820b-73fd-8701-1b34ab3769d0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-75b2-83c8-d9754d273056" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_01a139dd-820b-73fd-8701-1b34ab3769d0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_01a139dd-255d-7340-8bf4-c3d869d5808f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-75b2-83c8-d9754d273056" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_01a139dd-255d-7340-8bf4-c3d869d5808f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_01a081e7-21cb-7f33-baba-f034525ac2e8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-75b2-83c8-d9754d273056" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_01a081e7-21cb-7f33-baba-f034525ac2e8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_01a081e7-21cb-7f05-bf65-6790d1150e04" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-75b2-83c8-d9754d273056" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_01a081e7-21cb-7f05-bf65-6790d1150e04" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_01a081e7-21cb-7154-b81b-e28f028230f1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-75b2-83c8-d9754d273056" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_01a081e7-21cb-7154-b81b-e28f028230f1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_01a081e7-21cb-7659-b772-b1eb56aa55f4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01a081e7-21cb-75b2-83c8-d9754d273056" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_01a081e7-21cb-7659-b772-b1eb56aa55f4" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/NETLOSSPERSHAREScheduleofAntidilutiveSharesExcludedfromComputationofDilutedNetLossperShareDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#NETLOSSPERSHAREScheduleofAntidilutiveSharesExcludedfromComputationofDilutedNetLossperShareDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/NETLOSSPERSHAREScheduleofAntidilutiveSharesExcludedfromComputationofDilutedNetLossperShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_01a081e7-21cb-7cfc-a90b-2fc93aa80850" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_01a081e7-21cb-707e-baa8-68671d279323" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_01a081e7-21cb-7cfc-a90b-2fc93aa80850" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_01a081e7-21cb-707e-baa8-68671d279323" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_01a081e7-21cb-7111-a776-deff462f8675" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_01a081e7-21cb-707e-baa8-68671d279323" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_01a081e7-21cb-7111-a776-deff462f8675" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a081e7-21cb-7111-a776-deff462f8675_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_01a081e7-21cb-7111-a776-deff462f8675" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a081e7-21cb-7111-a776-deff462f8675_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a081e7-21cb-7870-a744-214ec02394fc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_01a081e7-21cb-7111-a776-deff462f8675" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a081e7-21cb-7870-a744-214ec02394fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtSecuritiesMember_01a081e7-21cb-7b79-bc6c-e139f66f19ab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a081e7-21cb-7870-a744-214ec02394fc" xlink:to="loc_us-gaap_ConvertibleDebtSecuritiesMember_01a081e7-21cb-7b79-bc6c-e139f66f19ab" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockCompensationPlanMember_01a081e7-21cb-7d4a-86c1-841e2e446b31" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockCompensationPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a081e7-21cb-7870-a744-214ec02394fc" xlink:to="loc_us-gaap_StockCompensationPlanMember_01a081e7-21cb-7d4a-86c1-841e2e446b31" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_01a081e7-21cb-737b-8f3e-1026f47d27be" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_01a081e7-21cb-7cfc-a90b-2fc93aa80850" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_01a081e7-21cb-737b-8f3e-1026f47d27be" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/SEGMENTANDGEOGRAPHICINFORMATIONScheduleofSegmentProfitorLossDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#SEGMENTANDGEOGRAPHICINFORMATIONScheduleofSegmentProfitorLossDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/SEGMENTANDGEOGRAPHICINFORMATIONScheduleofSegmentProfitorLossDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_01a081e7-21cb-70a8-8d85-13e6a4d47173" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_01a081e7-21cb-70ad-86d9-4ff818637c3e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_01a081e7-21cb-70a8-8d85-13e6a4d47173" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_01a081e7-21cb-70ad-86d9-4ff818637c3e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_01a081e7-21cb-714c-a838-61767393c986" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_01a081e7-21cb-70ad-86d9-4ff818637c3e" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_01a081e7-21cb-714c-a838-61767393c986" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_01a081e7-21cb-714c-a838-61767393c986_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_01a081e7-21cb-714c-a838-61767393c986" xlink:to="loc_us-gaap_SegmentDomain_01a081e7-21cb-714c-a838-61767393c986_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_01a081e7-21cb-7d55-999e-0acbe916332a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_01a081e7-21cb-714c-a838-61767393c986" xlink:to="loc_us-gaap_SegmentDomain_01a081e7-21cb-7d55-999e-0acbe916332a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ReportableSegmentMember_01a081e7-21cb-72d4-98f7-2b65c3e34ffa" xlink:href="pacb-20260930.xsd#pacb_ReportableSegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_01a081e7-21cb-7d55-999e-0acbe916332a" xlink:to="loc_pacb_ReportableSegmentMember_01a081e7-21cb-72d4-98f7-2b65c3e34ffa" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_01a081e7-21cb-7e7f-ac9b-63ca9eefb059" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_01a081e7-21cb-70a8-8d85-13e6a4d47173" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_01a081e7-21cb-7e7f-ac9b-63ca9eefb059" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_01a081e7-21cb-70a8-8d85-13e6a4d47173" xlink:to="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfRevenue_01a081e7-21cb-79b3-89dc-810b65f21639" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostOfRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:to="loc_us-gaap_CostOfRevenue_01a081e7-21cb-79b3-89dc-810b65f21639" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_01a081e7-21cb-7f12-a880-265a483678aa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_01a081e7-21cb-7f12-a880-265a483678aa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingAndMarketingExpense_01a081e7-21cb-78b6-a09c-86a83e3949b5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SellingAndMarketingExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:to="loc_us-gaap_SellingAndMarketingExpense_01a081e7-21cb-78b6-a09c-86a83e3949b5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_01a081e7-21cb-7bac-ab26-85fa02ba8e98" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_01a081e7-21cb-7bac-ab26-85fa02ba8e98" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21cb-7b80-8ac8-d729499baf6e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillAndIntangibleAssetImpairment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:to="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a081e7-21cb-7b80-8ac8-d729499baf6e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_SettlementCharges_01a081e7-21cb-79b5-bc5a-fa8bbb5f1d9d" xlink:href="pacb-20260930.xsd#pacb_SettlementCharges"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:to="loc_pacb_SettlementCharges_01a081e7-21cb-79b5-bc5a-fa8bbb5f1d9d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnDispositionOfAssets1_01a081e7-21cb-7ebe-b8d2-a496b7b4e011" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GainLossOnDispositionOfAssets1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:to="loc_us-gaap_GainLossOnDispositionOfAssets1_01a081e7-21cb-7ebe-b8d2-a496b7b4e011" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_01a081e7-21cb-7865-8320-81fc57d4dbf2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_01a081e7-21cb-7865-8320-81fc57d4dbf2" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfIntangibleAssets_01a081e7-21cb-7e94-9b90-082d19827fbf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AmortizationOfIntangibleAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:to="loc_us-gaap_AmortizationOfIntangibleAssets_01a081e7-21cb-7e94-9b90-082d19827fbf" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_01a081e7-21cb-7373-85c9-2435503aed5d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationFromSegmentTotalsToConsolidatedAbstract_01a081e7-21cb-70a8-baa9-43da158a81bb" xlink:to="loc_us-gaap_OperatingIncomeLoss_01a081e7-21cb-7373-85c9-2435503aed5d" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_01a081e7-21cb-7bb9-8029-e1f37e224ce5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_01a081e7-21cb-70a8-8d85-13e6a4d47173" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_01a081e7-21cb-7bb9-8029-e1f37e224ce5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_01a081e7-21cb-7096-bfd1-1a7dfb815db0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_01a081e7-21cb-70a8-8d85-13e6a4d47173" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_01a081e7-21cb-7096-bfd1-1a7dfb815db0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_01a081e7-21cb-7742-9e8a-df2ac024f186" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_01a081e7-21cb-70a8-8d85-13e6a4d47173" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_01a081e7-21cb-7742-9e8a-df2ac024f186" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_01a081e7-21cb-7a28-9a0c-3bc4060ac4ac" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_01a081e7-21cb-70a8-8d85-13e6a4d47173" xlink:to="loc_us-gaap_NetIncomeLoss_01a081e7-21cb-7a28-9a0c-3bc4060ac4ac" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/SEGMENTANDGEOGRAPHICINFORMATIONScheduleofRevenuebyGeographicLocationDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#SEGMENTANDGEOGRAPHICINFORMATIONScheduleofRevenuebyGeographicLocationDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/SEGMENTANDGEOGRAPHICINFORMATIONScheduleofRevenuebyGeographicLocationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems_01a081e7-21cb-7762-ac80-3361f0c164aa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable_01a081e7-21cb-75f3-8209-af428f950556" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems_01a081e7-21cb-7762-ac80-3361f0c164aa" xlink:to="loc_us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable_01a081e7-21cb-75f3-8209-af428f950556" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_01a081e7-21cb-7873-8bf5-6fbca3296517" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable_01a081e7-21cb-75f3-8209-af428f950556" xlink:to="loc_srt_StatementGeographicalAxis_01a081e7-21cb-7873-8bf5-6fbca3296517" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_01a081e7-21cb-7873-8bf5-6fbca3296517_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_01a081e7-21cb-7873-8bf5-6fbca3296517" xlink:to="loc_srt_SegmentGeographicalDomain_01a081e7-21cb-7873-8bf5-6fbca3296517_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_01a081e7-21cb-7cce-8e82-c4a2e603162b" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_01a081e7-21cb-7873-8bf5-6fbca3296517" xlink:to="loc_srt_SegmentGeographicalDomain_01a081e7-21cb-7cce-8e82-c4a2e603162b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_AmericasMember_01a081e7-21cb-7793-9a6a-5e73f5f9f9dd" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_AmericasMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_01a081e7-21cb-7cce-8e82-c4a2e603162b" xlink:to="loc_srt_AmericasMember_01a081e7-21cb-7793-9a6a-5e73f5f9f9dd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EMEAMember_01a081e7-21cb-7183-8a94-a18b480762d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EMEAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_01a081e7-21cb-7cce-8e82-c4a2e603162b" xlink:to="loc_us-gaap_EMEAMember_01a081e7-21cb-7183-8a94-a18b480762d7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_AsiaPacificMember_01a081e7-21cb-7fd2-bb4c-b1e4f92ce0f3" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_AsiaPacificMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_01a081e7-21cb-7cce-8e82-c4a2e603162b" xlink:to="loc_srt_AsiaPacificMember_01a081e7-21cb-7fd2-bb4c-b1e4f92ce0f3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_01a081e7-21cb-7457-9e22-7de7c3dfd069" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems_01a081e7-21cb-7762-ac80-3361f0c164aa" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_01a081e7-21cb-7457-9e22-7de7c3dfd069" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pacificbiosciences.com/role/SEGMENTANDGEOGRAPHICINFORMATIONScheduleofRevenuebyCategoryDetails" xlink:type="simple" xlink:href="pacb-20260930.xsd#SEGMENTANDGEOGRAPHICINFORMATIONScheduleofRevenuebyCategoryDetails"/>
  <link:definitionLink xlink:role="http://www.pacificbiosciences.com/role/SEGMENTANDGEOGRAPHICINFORMATIONScheduleofRevenuebyCategoryDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems_01a081e7-21cb-7cab-98ed-299c6290443b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable_01a081e7-21cb-78bc-a798-7959491c5e24" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems_01a081e7-21cb-7cab-98ed-299c6290443b" xlink:to="loc_us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable_01a081e7-21cb-78bc-a798-7959491c5e24" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a081e7-21cb-7953-8a88-36812701445a" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable_01a081e7-21cb-78bc-a798-7959491c5e24" xlink:to="loc_srt_ProductOrServiceAxis_01a081e7-21cb-7953-8a88-36812701445a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21cb-7953-8a88-36812701445a_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21cb-7953-8a88-36812701445a" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21cb-7953-8a88-36812701445a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a081e7-21cb-7673-be27-444a468d66fe" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a081e7-21cb-7953-8a88-36812701445a" xlink:to="loc_srt_ProductsAndServicesDomain_01a081e7-21cb-7673-be27-444a468d66fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_01a081e7-21cb-7371-b9a8-e2460054ee34" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a081e7-21cb-7673-be27-444a468d66fe" xlink:to="loc_us-gaap_ProductMember_01a081e7-21cb-7371-b9a8-e2460054ee34" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_InstrumentMember_01a081e7-21cb-7c3e-8d74-89a6ef1a6ae1" xlink:href="pacb-20260930.xsd#pacb_InstrumentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_01a081e7-21cb-7371-b9a8-e2460054ee34" xlink:to="loc_pacb_InstrumentMember_01a081e7-21cb-7c3e-8d74-89a6ef1a6ae1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ConsumablesMember_01a081e7-21cb-7023-8b1e-815d344a62d4" xlink:href="pacb-20260930.xsd#pacb_ConsumablesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ProductMember_01a081e7-21cb-7371-b9a8-e2460054ee34" xlink:to="loc_pacb_ConsumablesMember_01a081e7-21cb-7023-8b1e-815d344a62d4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_pacb_ServiceAndOtherMember_01a081e7-21cb-78cc-92f4-b637ae82aaf3" xlink:href="pacb-20260930.xsd#pacb_ServiceAndOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a081e7-21cb-7673-be27-444a468d66fe" xlink:to="loc_pacb_ServiceAndOtherMember_01a081e7-21cb-78cc-92f4-b637ae82aaf3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_01a081e7-21cb-7b0c-bf82-b37d2cd7dd05" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems_01a081e7-21cb-7cab-98ed-299c6290443b" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_01a081e7-21cb-7b0c-bf82-b37d2cd7dd05" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
