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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019ebbf8-0bf5-7898-b29f-e789e21cdc98,g:dad34a4d-e33f-4d93-aa23-4cf272e4291f-->
<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" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="https://xbrl.org/2023/arcrole/summation-item" xlink:type="simple" xlink:href="https://www.xbrl.org/2023/calculation-1.1.xsd#summation-item"/>
  <link:roleRef roleURI="http://www.zymeworks.com/role/CondensedConsolidatedBalanceSheets" xlink:type="simple" xlink:href="zyme-20260630.xsd#CondensedConsolidatedBalanceSheets"/>
  <link:calculationLink xlink:role="http://www.zymeworks.com/role/CondensedConsolidatedBalanceSheets" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_019ebbf8-0cad-7fb9-b065-066a2be5a81a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_019ebbf8-0cad-7186-aaa6-bbe5e6971416" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Liabilities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_019ebbf8-0cad-7fb9-b065-066a2be5a81a" xlink:to="loc_us-gaap_Liabilities_019ebbf8-0cad-7186-aaa6-bbe5e6971416" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019ebbf8-0cad-7da1-a384-3dd23fc720d9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_019ebbf8-0cad-7fb9-b065-066a2be5a81a" xlink:to="loc_us-gaap_StockholdersEquity_019ebbf8-0cad-7da1-a384-3dd23fc720d9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_019ebbf8-0cad-7cad-a144-ddba0de39e53" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019ebbf8-0cad-77bc-b26e-c269a3d4267c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019ebbf8-0cad-7cad-a144-ddba0de39e53" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019ebbf8-0cad-77bc-b26e-c269a3d4267c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestCurrent_019ebbf8-0cad-73b1-9236-61e855c6512f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019ebbf8-0cad-7cad-a144-ddba0de39e53" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestCurrent_019ebbf8-0cad-73b1-9236-61e855c6512f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_019ebbf8-0cad-7b1b-9cf8-9ff0060177e5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019ebbf8-0cad-7cad-a144-ddba0de39e53" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_019ebbf8-0cad-7b1b-9cf8-9ff0060177e5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_019ebbf8-0cad-7fb9-9abc-bfe262baf298" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_019ebbf8-0cad-7cad-a144-ddba0de39e53" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_019ebbf8-0cad-7fb9-9abc-bfe262baf298" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_019ebbf8-0cad-703d-b87a-3bac5438a0b9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_019ebbf8-0cad-74fc-9508-8be0c14fb07d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019ebbf8-0cad-703d-b87a-3bac5438a0b9" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_019ebbf8-0cad-74fc-9508-8be0c14fb07d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_019ebbf8-0cad-71de-abef-365cc6a82de3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Goodwill"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019ebbf8-0cad-703d-b87a-3bac5438a0b9" xlink:to="loc_us-gaap_Goodwill_019ebbf8-0cad-71de-abef-365cc6a82de3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019ebbf8-0cad-71c0-92b4-c59694c7e411" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019ebbf8-0cad-703d-b87a-3bac5438a0b9" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_019ebbf8-0cad-71c0-92b4-c59694c7e411" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxAssetsNet_019ebbf8-0cad-705b-a397-a171a160b0ab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DeferredIncomeTaxAssetsNet"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019ebbf8-0cad-703d-b87a-3bac5438a0b9" xlink:to="loc_us-gaap_DeferredIncomeTaxAssetsNet_019ebbf8-0cad-705b-a397-a171a160b0ab" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_019ebbf8-0cad-7b84-a313-fe10cb080f18" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019ebbf8-0cad-703d-b87a-3bac5438a0b9" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_019ebbf8-0cad-7b84-a313-fe10cb080f18" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestNoncurrent_019ebbf8-0cad-72cd-a864-54be428355fe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestNoncurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019ebbf8-0cad-703d-b87a-3bac5438a0b9" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterestNoncurrent_019ebbf8-0cad-72cd-a864-54be428355fe" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsNoncurrent_019ebbf8-0cad-7719-a8ca-4f75e49f2ae7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PrepaidExpenseAndOtherAssetsNoncurrent"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019ebbf8-0cad-703d-b87a-3bac5438a0b9" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssetsNoncurrent_019ebbf8-0cad-7719-a8ca-4f75e49f2ae7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_019ebbf8-0cad-7abb-b9cf-1cd38da441fb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_019ebbf8-0cad-703d-b87a-3bac5438a0b9" xlink:to="loc_us-gaap_AssetsCurrent_019ebbf8-0cad-7abb-b9cf-1cd38da441fb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_019ebbf8-0cad-7fb2-924c-766603658be6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_019ebbf8-0cad-72e0-bb39-4034923f7b1b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019ebbf8-0cad-7fb2-924c-766603658be6" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_019ebbf8-0cad-72e0-bb39-4034923f7b1b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_019ebbf8-0cad-71d1-99fc-da72538994e9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019ebbf8-0cad-7fb2-924c-766603658be6" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_019ebbf8-0cad-71d1-99fc-da72538994e9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedIncomeTaxesCurrent_019ebbf8-0cad-7ee7-8e27-51c607738d2c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccruedIncomeTaxesCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019ebbf8-0cad-7fb2-924c-766603658be6" xlink:to="loc_us-gaap_AccruedIncomeTaxesCurrent_019ebbf8-0cad-7ee7-8e27-51c607738d2c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableAndAccruedLiabilitiesCurrent_019ebbf8-0cad-720b-ac17-eb6ce3180971" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccountsPayableAndAccruedLiabilitiesCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_019ebbf8-0cad-7fb2-924c-766603658be6" xlink:to="loc_us-gaap_AccountsPayableAndAccruedLiabilitiesCurrent_019ebbf8-0cad-720b-ac17-eb6ce3180971" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_019ebbf8-0cad-7fbb-889f-280ffb2645c2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Liabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_019ebbf8-0cad-77e2-88bf-83062aaf5226" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019ebbf8-0cad-7fbb-889f-280ffb2645c2" xlink:to="loc_us-gaap_LiabilitiesCurrent_019ebbf8-0cad-77e2-88bf-83062aaf5226" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_019ebbf8-0cad-7602-919c-f23ea987a57b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019ebbf8-0cad-7fbb-889f-280ffb2645c2" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_019ebbf8-0cad-7602-919c-f23ea987a57b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_019ebbf8-0cad-78d1-a80e-844bc8e40f34" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019ebbf8-0cad-7fbb-889f-280ffb2645c2" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_019ebbf8-0cad-78d1-a80e-844bc8e40f34" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_AccruedSaleOfFutureRoyalties_019ebbf8-0cad-7dbd-a33f-4b8539f6e497" xlink:href="zyme-20260630.xsd#zyme_AccruedSaleOfFutureRoyalties"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019ebbf8-0cad-7fbb-889f-280ffb2645c2" xlink:to="loc_zyme_AccruedSaleOfFutureRoyalties_019ebbf8-0cad-7dbd-a33f-4b8539f6e497" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_019ebbf8-0cad-7b15-8a22-4a2a2b25180e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019ebbf8-0cad-7fbb-889f-280ffb2645c2" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_019ebbf8-0cad-7b15-8a22-4a2a2b25180e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncomeTaxLiabilitiesNet_019ebbf8-0cad-7081-8ea3-76c5a60d34f1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DeferredIncomeTaxLiabilitiesNet"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_019ebbf8-0cad-7fbb-889f-280ffb2645c2" xlink:to="loc_us-gaap_DeferredIncomeTaxLiabilitiesNet_019ebbf8-0cad-7081-8ea3-76c5a60d34f1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019ebbf8-0cad-78d0-8315-bd69b68f9a3f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_019ebbf8-0cad-702e-8d8e-c6a9472a6097" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019ebbf8-0cad-78d0-8315-bd69b68f9a3f" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_019ebbf8-0cad-702e-8d8e-c6a9472a6097" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_019ebbf8-0cad-778c-b55e-01f9e38d361e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019ebbf8-0cad-78d0-8315-bd69b68f9a3f" xlink:to="loc_us-gaap_CommonStockValue_019ebbf8-0cad-778c-b55e-01f9e38d361e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_019ebbf8-0cad-7c88-9609-b05334718f79" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019ebbf8-0cad-78d0-8315-bd69b68f9a3f" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_019ebbf8-0cad-7c88-9609-b05334718f79" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_ExchangeableSharesValueIssued_019ebbf8-0cad-7ddd-97e5-2f95c9efdf90" xlink:href="zyme-20260630.xsd#zyme_ExchangeableSharesValueIssued"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019ebbf8-0cad-78d0-8315-bd69b68f9a3f" xlink:to="loc_zyme_ExchangeableSharesValueIssued_019ebbf8-0cad-7ddd-97e5-2f95c9efdf90" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalCommonStock_019ebbf8-0cad-7510-a747-c968a67f3ae6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdditionalPaidInCapitalCommonStock"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019ebbf8-0cad-78d0-8315-bd69b68f9a3f" xlink:to="loc_us-gaap_AdditionalPaidInCapitalCommonStock_019ebbf8-0cad-7510-a747-c968a67f3ae6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockValue_019ebbf8-0cad-758f-995a-5151a78c8c97" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockValue"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_019ebbf8-0cad-78d0-8315-bd69b68f9a3f" xlink:to="loc_us-gaap_PreferredStockValue_019ebbf8-0cad-758f-995a-5151a78c8c97" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.zymeworks.com/role/CondensedConsolidatedStatementsofLossIncomeandComprehensiveLossIncome" xlink:type="simple" xlink:href="zyme-20260630.xsd#CondensedConsolidatedStatementsofLossIncomeandComprehensiveLossIncome"/>
  <link:calculationLink xlink:role="http://www.zymeworks.com/role/CondensedConsolidatedStatementsofLossIncomeandComprehensiveLossIncome" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019ebbf8-0cad-75cf-96d9-dc8ab33f5e3d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_019ebbf8-0cad-7286-815c-89aec79960d2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_019ebbf8-0cad-75cf-96d9-dc8ab33f5e3d" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_019ebbf8-0cad-7286-815c-89aec79960d2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019ebbf8-0cad-7114-86f3-0347c8d4667e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_019ebbf8-0cad-75cf-96d9-dc8ab33f5e3d" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019ebbf8-0cad-7114-86f3-0347c8d4667e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherOperatingIncomeExpenseNet_019ebbf8-0cad-78f0-beb3-db5e7366e54e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherOperatingIncomeExpenseNet"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestIncomeExpenseNonoperatingNet_019ebbf8-0cad-70fe-a973-3bb53d04b808" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestIncomeExpenseNonoperatingNet"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OtherOperatingIncomeExpenseNet_019ebbf8-0cad-78f0-beb3-db5e7366e54e" xlink:to="loc_us-gaap_InterestIncomeExpenseNonoperatingNet_019ebbf8-0cad-70fe-a973-3bb53d04b808" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_InterestExpenseAndAmortizationRelatedToSaleOfFutureRoyalties_019ebbf8-0cad-70e7-96a2-37625a56246d" xlink:href="zyme-20260630.xsd#zyme_InterestExpenseAndAmortizationRelatedToSaleOfFutureRoyalties"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OtherOperatingIncomeExpenseNet_019ebbf8-0cad-78f0-beb3-db5e7366e54e" xlink:to="loc_zyme_InterestExpenseAndAmortizationRelatedToSaleOfFutureRoyalties_019ebbf8-0cad-70e7-96a2-37625a56246d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_019ebbf8-0cad-7b80-8e7f-47b03c4055e5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OtherOperatingIncomeExpenseNet_019ebbf8-0cad-78f0-beb3-db5e7366e54e" xlink:to="loc_us-gaap_NonoperatingIncomeExpense_019ebbf8-0cad-7b80-8e7f-47b03c4055e5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_019ebbf8-0cad-7f18-a3ce-b011915c7fe2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019ebbf8-0cad-7d15-b084-5e4c04e789f4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_019ebbf8-0cad-7f18-a3ce-b011915c7fe2" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019ebbf8-0cad-7d15-b084-5e4c04e789f4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_019ebbf8-0cad-7a7c-9376-bb965c9e2f76" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostsAndExpenses"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_019ebbf8-0cad-7f18-a3ce-b011915c7fe2" xlink:to="loc_us-gaap_CostsAndExpenses_019ebbf8-0cad-7a7c-9376-bb965c9e2f76" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_019ebbf8-0cad-7c53-aeb8-09c608f7e2c7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_019ebbf8-0cad-7945-813b-76e92b069ce0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_019ebbf8-0cad-7c53-aeb8-09c608f7e2c7" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_019ebbf8-0cad-7945-813b-76e92b069ce0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019ebbf8-0cad-7107-8a86-da4211df8689" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_019ebbf8-0cad-7c53-aeb8-09c608f7e2c7" xlink:to="loc_us-gaap_NetIncomeLoss_019ebbf8-0cad-7107-8a86-da4211df8689" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_019ebbf8-0cad-7b0f-a093-9892ff78d7ce" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostsAndExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost_019ebbf8-0cad-79b0-9df6-6aa3f1430f1d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_019ebbf8-0cad-7b0f-a093-9892ff78d7ce" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost_019ebbf8-0cad-79b0-9df6-6aa3f1430f1d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_019ebbf8-0cad-7189-be63-648bd88082d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_019ebbf8-0cad-7b0f-a093-9892ff78d7ce" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_019ebbf8-0cad-7189-be63-648bd88082d7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019ebbf8-0cad-7ae1-869c-5bc818f5f0ae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_019ebbf8-0cad-7381-b587-6b2044cc8d30" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019ebbf8-0cad-7ae1-869c-5bc818f5f0ae" xlink:to="loc_us-gaap_OperatingIncomeLoss_019ebbf8-0cad-7381-b587-6b2044cc8d30" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherOperatingIncomeExpenseNet_019ebbf8-0cad-7f4b-b356-85665ae43131" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherOperatingIncomeExpenseNet"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019ebbf8-0cad-7ae1-869c-5bc818f5f0ae" xlink:to="loc_us-gaap_OtherOperatingIncomeExpenseNet_019ebbf8-0cad-7f4b-b356-85665ae43131" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_019ebbf8-0cad-7f2f-8fc9-335242e29761" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_019ebbf8-0cad-7094-beb7-6ce86ba5eb44" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_019ebbf8-0cad-7f2f-8fc9-335242e29761" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_019ebbf8-0cad-7094-beb7-6ce86ba5eb44" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.zymeworks.com/role/CondensedConsolidatedStatementsofCashFlows" xlink:type="simple" xlink:href="zyme-20260630.xsd#CondensedConsolidatedStatementsofCashFlows"/>
  <link:calculationLink xlink:role="http://www.zymeworks.com/role/CondensedConsolidatedStatementsofCashFlows" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019ebbf8-0cad-775a-8b85-b1ac0faac348" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireMarketableSecurities_019ebbf8-0cad-752a-9f54-6bc3f1f4c4f3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireMarketableSecurities"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019ebbf8-0cad-775a-8b85-b1ac0faac348" xlink:to="loc_us-gaap_PaymentsToAcquireMarketableSecurities_019ebbf8-0cad-752a-9f54-6bc3f1f4c4f3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities_019ebbf8-0cad-737c-85fd-397c323aaeda" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019ebbf8-0cad-775a-8b85-b1ac0faac348" xlink:to="loc_us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities_019ebbf8-0cad-737c-85fd-397c323aaeda" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_019ebbf8-0cad-7e0d-ab42-1e853e375ca1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019ebbf8-0cad-775a-8b85-b1ac0faac348" xlink:to="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_019ebbf8-0cad-7e0d-ab42-1e853e375ca1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireIntangibleAssets_019ebbf8-0cad-7caa-b845-b89890daa81d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireIntangibleAssets"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019ebbf8-0cad-775a-8b85-b1ac0faac348" xlink:to="loc_us-gaap_PaymentsToAcquireIntangibleAssets_019ebbf8-0cad-7caa-b845-b89890daa81d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019ebbf8-0cad-72ad-bd26-510f3dc901fe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_019ebbf8-0cad-7c7f-9290-00f8e0aba693" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019ebbf8-0cad-72ad-bd26-510f3dc901fe" xlink:to="loc_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_019ebbf8-0cad-7c7f-9290-00f8e0aba693" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019ebbf8-0cad-7ffa-9126-d2322f076746" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019ebbf8-0cad-72ad-bd26-510f3dc901fe" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_019ebbf8-0cad-7ffa-9126-d2322f076746" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019ebbf8-0cad-79a8-a33e-80c960c2296e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019ebbf8-0cad-72ad-bd26-510f3dc901fe" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019ebbf8-0cad-79a8-a33e-80c960c2296e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-7341-b81d-38c760f1c50b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_019ebbf8-0cad-72ad-bd26-510f3dc901fe" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-7341-b81d-38c760f1c50b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019ebbf8-0cad-7a93-935a-bd050541309a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_NetIncomeLoss_019ebbf8-0cad-7a93-935a-bd050541309a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Depreciation_019ebbf8-0cad-7c68-a927-675283c140e4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Depreciation"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_Depreciation_019ebbf8-0cad-7c68-a927-675283c140e4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfIntangibleAssets_019ebbf8-0cad-70f9-9346-5140ca1b270e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AmortizationOfIntangibleAssets"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_AmortizationOfIntangibleAssets_019ebbf8-0cad-70f9-9346-5140ca1b270e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_019ebbf8-0cad-7af5-a16c-de04cd94a1d8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_ShareBasedCompensation_019ebbf8-0cad-7af5-a16c-de04cd94a1d8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_019ebbf8-0cad-70ee-a670-b8d7252e2a45" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_019ebbf8-0cad-70ee-a670-b8d7252e2a45" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCosts_019ebbf8-0cad-790c-a6e2-a6b6333a9e60" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AmortizationOfFinancingCosts"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_AmortizationOfFinancingCosts_019ebbf8-0cad-790c-a6e2-a6b6333a9e60" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_NonCashInterestExpenseRelatedToSaleOfRoyalties_019ebbf8-0cad-70b0-a597-0af103fee2c8" xlink:href="zyme-20260630.xsd#zyme_NonCashInterestExpenseRelatedToSaleOfRoyalties"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_zyme_NonCashInterestExpenseRelatedToSaleOfRoyalties_019ebbf8-0cad-70b0-a597-0af103fee2c8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInDeferredIncomeTaxes_019ebbf8-0cad-7299-9308-97e117e81ee0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInDeferredIncomeTaxes"/>
    <link:calculationArc order="8" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_IncreaseDecreaseInDeferredIncomeTaxes_019ebbf8-0cad-7299-9308-97e117e81ee0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForeignCurrencyTransactionGainLossUnrealized_019ebbf8-0cad-7466-a0fb-27899a16c69e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ForeignCurrencyTransactionGainLossUnrealized"/>
    <link:calculationArc order="9" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_ForeignCurrencyTransactionGainLossUnrealized_019ebbf8-0cad-7466-a0fb-27899a16c69e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_019ebbf8-0cad-72e1-8496-b6d07eb8ae38" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable"/>
    <link:calculationArc order="10" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_019ebbf8-0cad-72e1-8496-b6d07eb8ae38" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_019ebbf8-0cad-7944-8639-acf2139dec66" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets"/>
    <link:calculationArc order="11" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_019ebbf8-0cad-7944-8639-acf2139dec66" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities_019ebbf8-0cad-7e9a-8643-4c809d41e3c8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities"/>
    <link:calculationArc order="12" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities_019ebbf8-0cad-7e9a-8643-4c809d41e3c8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_IncreaseDecreaseInOperatingLeaseLiabilities_019ebbf8-0cad-7e55-84c3-53c7fb5420ec" xlink:href="zyme-20260630.xsd#zyme_IncreaseDecreaseInOperatingLeaseLiabilities"/>
    <link:calculationArc order="13" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_zyme_IncreaseDecreaseInOperatingLeaseLiabilities_019ebbf8-0cad-7e55-84c3-53c7fb5420ec" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_019ebbf8-0cad-7d95-a6d0-04ce81c98174" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability"/>
    <link:calculationArc order="14" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_019ebbf8-0cad-7d95-a6d0-04ce81c98174" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_019ebbf8-0cad-7315-a513-82951b69cd3e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable"/>
    <link:calculationArc order="15" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable_019ebbf8-0cad-7315-a513-82951b69cd3e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_NonCashRoyaltyRevenueRelatedToSaleOfRoyalties_019f82ad-94dc-7f54-8c60-6b63bf1c7a24" xlink:href="zyme-20260630.xsd#zyme_NonCashRoyaltyRevenueRelatedToSaleOfRoyalties"/>
    <link:calculationArc order="16" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_019ebbf8-0cad-782f-b05c-acd927ec3a7d" xlink:to="loc_zyme_NonCashRoyaltyRevenueRelatedToSaleOfRoyalties_019f82ad-94dc-7f54-8c60-6b63bf1c7a24" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019ebbf8-0cad-74b0-aaea-5a79bcce4517" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_019ebbf8-0cad-77e7-a274-38b0aeed7420" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019ebbf8-0cad-74b0-aaea-5a79bcce4517" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions_019ebbf8-0cad-77e7-a274-38b0aeed7420" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_ProceedsFromIssuanceOfSharesUnderEmployeeSharePurchasePlan_019ebbf8-0cad-70d1-beaa-710798513e88" xlink:href="zyme-20260630.xsd#zyme_ProceedsFromIssuanceOfSharesUnderEmployeeSharePurchasePlan"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019ebbf8-0cad-74b0-aaea-5a79bcce4517" xlink:to="loc_zyme_ProceedsFromIssuanceOfSharesUnderEmployeeSharePurchasePlan_019ebbf8-0cad-70d1-beaa-710798513e88" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_019ebbf8-0cad-77f1-84e7-e4172238de43" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019ebbf8-0cad-74b0-aaea-5a79bcce4517" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_019ebbf8-0cad-77f1-84e7-e4172238de43" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_ProceedsFromSaleOfFutureRoyalties_019ebbf8-0cad-7285-9daf-ab625250adb4" xlink:href="zyme-20260630.xsd#zyme_ProceedsFromSaleOfFutureRoyalties"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019ebbf8-0cad-74b0-aaea-5a79bcce4517" xlink:to="loc_zyme_ProceedsFromSaleOfFutureRoyalties_019ebbf8-0cad-7285-9daf-ab625250adb4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_019ebbf8-0cad-72d3-816d-68ec581218b5" xlink:href="zyme-20260630.xsd#zyme_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties"/>
    <link:calculationArc order="5" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019ebbf8-0cad-74b0-aaea-5a79bcce4517" xlink:to="loc_zyme_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_019ebbf8-0cad-72d3-816d-68ec581218b5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsOfFinancingCosts_019fa323-32e3-7f22-849e-3953fa533e14" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsOfFinancingCosts"/>
    <link:calculationArc order="6" weight="-1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_019ebbf8-0cad-74b0-aaea-5a79bcce4517" xlink:to="loc_us-gaap_PaymentsOfFinancingCosts_019fa323-32e3-7f22-849e-3953fa533e14" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.zymeworks.com/role/NetLossPerShareDetails" xlink:type="simple" xlink:href="zyme-20260630.xsd#NetLossPerShareDetails"/>
  <link:calculationLink xlink:role="http://www.zymeworks.com/role/NetLossPerShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_019ebbf8-0cae-73c6-89c5-b127e52f67c6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_019ebbf8-0cae-7525-b027-36531a9b3ef8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_019ebbf8-0cae-73c6-89c5-b127e52f67c6" xlink:to="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic_019ebbf8-0cae-7525-b027-36531a9b3ef8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_FairValueOptionAdjustmentForChangeInFairValueOfLiabilityClassifiedStockOptions_019ebbf8-0cae-7c7f-b362-1ebdbc3d3196" xlink:href="zyme-20260630.xsd#zyme_FairValueOptionAdjustmentForChangeInFairValueOfLiabilityClassifiedStockOptions"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted_019ebbf8-0cae-73c6-89c5-b127e52f67c6" xlink:to="loc_zyme_FairValueOptionAdjustmentForChangeInFairValueOfLiabilityClassifiedStockOptions_019ebbf8-0cae-7c7f-b362-1ebdbc3d3196" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019ebbf8-0cae-74ad-9076-f61d32021e23" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_019ebbf8-0cae-74b2-baeb-30200a2e306c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019ebbf8-0cae-74ad-9076-f61d32021e23" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_019ebbf8-0cae-74b2-baeb-30200a2e306c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_IncrementalCommonSharesAttributableToDilutiveEffectOfShareBasedPaymentArrangementsLiabilityClassified_019ebbf8-0cae-7731-ba32-8363e24b8cf6" xlink:href="zyme-20260630.xsd#zyme_IncrementalCommonSharesAttributableToDilutiveEffectOfShareBasedPaymentArrangementsLiabilityClassified"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019ebbf8-0cae-74ad-9076-f61d32021e23" xlink:to="loc_zyme_IncrementalCommonSharesAttributableToDilutiveEffectOfShareBasedPaymentArrangementsLiabilityClassified_019ebbf8-0cae-7731-ba32-8363e24b8cf6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_019eff9c-127c-748b-ba77-b01634d3d96a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019ebbf8-0cae-74ad-9076-f61d32021e23" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_019eff9c-127c-748b-ba77-b01634d3d96a" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.zymeworks.com/role/CashCashEquivalentsandMarketableSecuritiesScheduleofMarketableSecuritiesDetails" xlink:type="simple" xlink:href="zyme-20260630.xsd#CashCashEquivalentsandMarketableSecuritiesScheduleofMarketableSecuritiesDetails"/>
  <link:calculationLink xlink:role="http://www.zymeworks.com/role/CashCashEquivalentsandMarketableSecuritiesScheduleofMarketableSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedGainLoss_019ebbf8-0cae-730c-9f12-d75209d056a3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedGainLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateYearOne_019ebbf8-0cae-7021-84be-784c6875e7f4" xlink:href="zyme-20260630.xsd#zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateYearOne"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedGainLoss_019ebbf8-0cae-730c-9f12-d75209d056a3" xlink:to="loc_zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateYearOne_019ebbf8-0cae-7021-84be-784c6875e7f4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughFour_019ebbf8-0cae-7141-8050-ff33c2d57cf5" xlink:href="zyme-20260630.xsd#zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughFour"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedGainLoss_019ebbf8-0cae-730c-9f12-d75209d056a3" xlink:to="loc_zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughFour_019ebbf8-0cae-7141-8050-ff33c2d57cf5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestBeforeAllowanceForCreditLoss_019ebbf8-0cae-7315-9605-fefb9e00e939" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestBeforeAllowanceForCreditLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearAmortizedCost_019ebbf8-0cae-7f4a-a17b-021c79b7f76f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearAmortizedCost"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestBeforeAllowanceForCreditLoss_019ebbf8-0cae-7315-9605-fefb9e00e939" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearAmortizedCost_019ebbf8-0cae-7f4a-a17b-021c79b7f76f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValueCost_019ebbf8-0cae-7eb4-bb2b-b22abef347ea" xlink:href="zyme-20260630.xsd#zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValueCost"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestBeforeAllowanceForCreditLoss_019ebbf8-0cae-7315-9605-fefb9e00e939" xlink:to="loc_zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValueCost_019ebbf8-0cae-7eb4-bb2b-b22abef347ea" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValue_019ebbf8-0cae-7f05-9216-22d330369c76" xlink:href="zyme-20260630.xsd#zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValue"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_DebtSecuritiesAvailableForSaleFairValueMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughThree_019ebbf8-0cae-7038-a62f-bf6c3154a9f5" xlink:href="zyme-20260630.xsd#zyme_DebtSecuritiesAvailableForSaleFairValueMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughThree"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValue_019ebbf8-0cae-7f05-9216-22d330369c76" xlink:to="loc_zyme_DebtSecuritiesAvailableForSaleFairValueMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughThree_019ebbf8-0cae-7038-a62f-bf6c3154a9f5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest_019ebbf8-0cae-77b3-9384-e76cf7dbc79a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValue_019ebbf8-0cae-71ce-b598-7d8a2bca7b8a" xlink:href="zyme-20260630.xsd#zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest_019ebbf8-0cae-77b3-9384-e76cf7dbc79a" xlink:to="loc_zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValue_019ebbf8-0cae-71ce-b598-7d8a2bca7b8a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue_019ebbf8-0cae-7531-aa34-07efe708ad9e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest_019ebbf8-0cae-77b3-9384-e76cf7dbc79a" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue_019ebbf8-0cae-7531-aa34-07efe708ad9e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughFour_019ebbf8-0cae-74b2-a5ac-d594ab649b9c" xlink:href="zyme-20260630.xsd#zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughFour"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughThree_019ebbf8-0cae-7aa3-a0b2-0a1645582faa" xlink:href="zyme-20260630.xsd#zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughThree"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughFour_019ebbf8-0cae-74b2-a5ac-d594ab649b9c" xlink:to="loc_zyme_DebtSecuritiesAvailableForSaleUnrealizedGainLossMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughThree_019ebbf8-0cae-7aa3-a0b2-0a1645582faa" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValueCost_019ebbf8-0cae-7857-8c7e-e76c9f49c23d" xlink:href="zyme-20260630.xsd#zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValueCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_zyme_DebtSecuritiesAvailableForSaleAmortizedCostMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughThree_019ebbf8-0cae-7918-9fe7-e344fdce292d" xlink:href="zyme-20260630.xsd#zyme_DebtSecuritiesAvailableForSaleAmortizedCostMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughThree"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_zyme_DebtSecuritiesAndEquitySecuritiesWithoutReadilyDeterminableFairValueCost_019ebbf8-0cae-7857-8c7e-e76c9f49c23d" xlink:to="loc_zyme_DebtSecuritiesAvailableForSaleAmortizedCostMaturityAllocatedAndSingleMaturityDateAfterYearOneThroughThree_019ebbf8-0cae-7918-9fe7-e344fdce292d" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.zymeworks.com/role/CashCashEquivalentsandMarketableSecuritiesScheduleofCashCashEquivalentsandMarketableSecuritiesMeasuredatFairValueonaRecurringBasisDetails" xlink:type="simple" xlink:href="zyme-20260630.xsd#CashCashEquivalentsandMarketableSecuritiesScheduleofCashCashEquivalentsandMarketableSecuritiesMeasuredatFairValueonaRecurringBasisDetails"/>
  <link:calculationLink xlink:role="http://www.zymeworks.com/role/CashCashEquivalentsandMarketableSecuritiesScheduleofCashCashEquivalentsandMarketableSecuritiesMeasuredatFairValueonaRecurringBasisDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_019ebbf8-0cae-7ebe-84f5-8013ee31157b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_019ebbf8-0cae-7d69-90f6-5ae91eac858b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_019ebbf8-0cae-7ebe-84f5-8013ee31157b" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_019ebbf8-0cae-7d69-90f6-5ae91eac858b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest_019ebbf8-0cae-73fd-b01c-8aa5358386cd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_019ebbf8-0cae-7ebe-84f5-8013ee31157b" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest_019ebbf8-0cae-73fd-b01c-8aa5358386cd" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.zymeworks.com/role/LeasesScheduleofBalanceSheetClassificationofLeaseLiabilitiesDetails" xlink:type="simple" xlink:href="zyme-20260630.xsd#LeasesScheduleofBalanceSheetClassificationofLeaseLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.zymeworks.com/role/LeasesScheduleofBalanceSheetClassificationofLeaseLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_019ebbf8-0d6d-7c2e-a667-b0e647c09f97" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_019ebbf8-0d6d-7fd2-9de3-588198f544a5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingLeaseLiability_019ebbf8-0d6d-7c2e-a667-b0e647c09f97" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_019ebbf8-0d6d-7fd2-9de3-588198f544a5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_019ebbf8-0d6d-75bc-8565-641d92513111" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingLeaseLiability_019ebbf8-0d6d-7c2e-a667-b0e647c09f97" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_019ebbf8-0d6d-75bc-8565-641d92513111" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.zymeworks.com/role/LeasesScheduleofMaturitiesofOperatingLeaseLiabilitiesDetails" xlink:type="simple" xlink:href="zyme-20260630.xsd#LeasesScheduleofMaturitiesofOperatingLeaseLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.zymeworks.com/role/LeasesScheduleofMaturitiesofOperatingLeaseLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019ebbf8-0d6d-7163-9fc7-3160df4f0182" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_019ebbf8-0d6d-7ba5-a37f-f9665c40df75" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019ebbf8-0d6d-7163-9fc7-3160df4f0182" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_019ebbf8-0d6d-7ba5-a37f-f9665c40df75" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiability_019ebbf8-0d6d-740f-9376-04c19ac9af8e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseLiability"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019ebbf8-0d6d-7163-9fc7-3160df4f0182" xlink:to="loc_us-gaap_OperatingLeaseLiability_019ebbf8-0d6d-740f-9376-04c19ac9af8e" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.zymeworks.com/role/LeasesScheduleofMaturitiesofOperatingLeaseLiabilitiesDetails_1" xlink:type="simple" xlink:href="zyme-20260630.xsd#LeasesScheduleofMaturitiesofOperatingLeaseLiabilitiesDetails_1"/>
  <link:calculationLink xlink:role="http://www.zymeworks.com/role/LeasesScheduleofMaturitiesofOperatingLeaseLiabilitiesDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019ebbf8-0d6d-7100-8800-ef2ddcc7cc8d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFour_019ebbf8-0d6d-7cad-abcc-48b027241bf6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFour"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019ebbf8-0d6d-7100-8800-ef2ddcc7cc8d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFour_019ebbf8-0d6d-7cad-abcc-48b027241bf6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFive_019ebbf8-0d6d-7487-b313-a005aca36783" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFive"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019ebbf8-0d6d-7100-8800-ef2ddcc7cc8d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearFive_019ebbf8-0d6d-7487-b313-a005aca36783" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterRollingYearFive_019ebbf8-0d6d-7b8c-9d4d-f63a6fd3f1a5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterRollingYearFive"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019ebbf8-0d6d-7100-8800-ef2ddcc7cc8d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterRollingYearFive_019ebbf8-0d6d-7b8c-9d4d-f63a6fd3f1a5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextRollingTwelveMonths_019ebbf8-0d6d-7773-b2cb-2b64b252d79a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextRollingTwelveMonths"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019ebbf8-0d6d-7100-8800-ef2ddcc7cc8d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextRollingTwelveMonths_019ebbf8-0d6d-7773-b2cb-2b64b252d79a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearTwo_019ebbf8-0d6d-7e6a-94a2-06f3764994f5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearTwo"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019ebbf8-0d6d-7100-8800-ef2ddcc7cc8d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearTwo_019ebbf8-0d6d-7e6a-94a2-06f3764994f5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearThree_019ebbf8-0d6d-746a-8cd0-991e7d390be4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearThree"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019ebbf8-0d6d-7100-8800-ef2ddcc7cc8d" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueInRollingYearThree_019ebbf8-0d6d-746a-8cd0-991e7d390be4" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.zymeworks.com/role/LeasesScheduleofCostComponentsofOperatingLeasesDetails" xlink:type="simple" xlink:href="zyme-20260630.xsd#LeasesScheduleofCostComponentsofOperatingLeasesDetails"/>
  <link:calculationLink xlink:role="http://www.zymeworks.com/role/LeasesScheduleofCostComponentsofOperatingLeasesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseCost_019ebbf8-0d6d-773b-b4cc-48452432c199" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LeaseCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseCost_019ebbf8-0d6d-740b-bdcb-b8ad7be610ae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingLeaseCost"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LeaseCost_019ebbf8-0d6d-773b-b4cc-48452432c199" xlink:to="loc_us-gaap_OperatingLeaseCost_019ebbf8-0d6d-740b-bdcb-b8ad7be610ae" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableLeaseCost_019ebbf8-0d6d-7303-afba-cf441c934042" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_VariableLeaseCost"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="https://xbrl.org/2023/arcrole/summation-item" xlink:from="loc_us-gaap_LeaseCost_019ebbf8-0d6d-773b-b4cc-48452432c199" xlink:to="loc_us-gaap_VariableLeaseCost_019ebbf8-0d6d-7303-afba-cf441c934042" xlink:type="arc"/>
  </link:calculationLink>
</link:linkbase>
