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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019cd38a-fc71-707a-a501-ed44139113af,g:e40782c3-91d2-44f3-a214-2a04140485f0-->
<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.schrodinger.com/role/Cover" xlink:type="simple" xlink:href="sdgr-20260331.xsd#Cover"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/Cover" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentInformationTable_019cd38a-fdd8-782e-b3ff-73ccd90aef45" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentInformationTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_DocumentInformationTable_019cd38a-fdd8-782e-b3ff-73ccd90aef45" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-71e4-906e-59db53c48f86" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_dei_DocumentInformationTable_019cd38a-fdd8-782e-b3ff-73ccd90aef45" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-71e4-906e-59db53c48f86" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-71e4-906e-59db53c48f86_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-71e4-906e-59db53c48f86" xlink:to="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-71e4-906e-59db53c48f86_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-76cc-aaad-5994767fb3f8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-71e4-906e-59db53c48f86" xlink:to="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-76cc-aaad-5994767fb3f8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_019cd38a-fdd8-7dad-b53b-648678963db0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-76cc-aaad-5994767fb3f8" xlink:to="loc_us-gaap_CommonStockMember_019cd38a-fdd8-7dad-b53b-648678963db0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_LimitedCommonStockMember_019cd38a-fdd8-7928-95d3-b5f0229df8ef" xlink:href="sdgr-20260331.xsd#sdgr_LimitedCommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-76cc-aaad-5994767fb3f8" xlink:to="loc_sdgr_LimitedCommonStockMember_019cd38a-fdd8-7928-95d3-b5f0229df8ef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentType_019cd38a-fdd8-7bfb-a8ca-369ce84cecd6" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentType"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_DocumentType_019cd38a-fdd8-7bfb-a8ca-369ce84cecd6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentQuarterlyReport_019cd38a-fdd8-799a-bd0e-c7e1abe9daba" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentQuarterlyReport"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_DocumentQuarterlyReport_019cd38a-fdd8-799a-bd0e-c7e1abe9daba" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentPeriodEndDate_019cd38a-fdd8-733e-a522-3585be5ee96f" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentPeriodEndDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_DocumentPeriodEndDate_019cd38a-fdd8-733e-a522-3585be5ee96f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentTransitionReport_019cd38a-fdd8-7697-a297-a6f941f85d7b" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentTransitionReport"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_DocumentTransitionReport_019cd38a-fdd8-7697-a297-a6f941f85d7b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFileNumber_019cd38a-fdd8-7ca4-9230-e6e39ac78182" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityFileNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityFileNumber_019cd38a-fdd8-7ca4-9230-e6e39ac78182" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityRegistrantName_019cd38a-fdd8-7096-a1a6-8045e17c013b" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityRegistrantName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityRegistrantName_019cd38a-fdd8-7096-a1a6-8045e17c013b" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityIncorporationStateCountryCode_019cd38a-fdd8-76ef-9213-65ed9ec8a354" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityIncorporationStateCountryCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityIncorporationStateCountryCode_019cd38a-fdd8-76ef-9213-65ed9ec8a354" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityTaxIdentificationNumber_019cd38a-fdd8-7c1c-b426-243bf7fbd7c0" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityTaxIdentificationNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityTaxIdentificationNumber_019cd38a-fdd8-7c1c-b426-243bf7fbd7c0" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressAddressLine1_019cd38a-fdd8-7f03-b247-dff1d3598cd5" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressAddressLine1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityAddressAddressLine1_019cd38a-fdd8-7f03-b247-dff1d3598cd5" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressAddressLine2_019cd38a-fdd8-78bc-93b0-3921ac084f77" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressAddressLine2"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityAddressAddressLine2_019cd38a-fdd8-78bc-93b0-3921ac084f77" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressCityOrTown_019cd38a-fdd8-71e1-aeec-2c5a17717236" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressCityOrTown"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityAddressCityOrTown_019cd38a-fdd8-71e1-aeec-2c5a17717236" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressStateOrProvince_019cd38a-fdd8-71c3-a3a1-b8148bdecccb" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressStateOrProvince"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityAddressStateOrProvince_019cd38a-fdd8-71c3-a3a1-b8148bdecccb" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressPostalZipCode_019cd38a-fdd8-70db-a4e2-03dccd35fd4b" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressPostalZipCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityAddressPostalZipCode_019cd38a-fdd8-70db-a4e2-03dccd35fd4b" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CityAreaCode_019cd38a-fdd8-7c24-99cf-6184c01fecc6" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_CityAreaCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_CityAreaCode_019cd38a-fdd8-7c24-99cf-6184c01fecc6" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LocalPhoneNumber_019cd38a-fdd8-77f3-994e-f2b9a137b7b9" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_LocalPhoneNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_LocalPhoneNumber_019cd38a-fdd8-77f3-994e-f2b9a137b7b9" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_Security12bTitle_019cd38a-fdd8-7148-a658-16d76486954f" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_Security12bTitle"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_Security12bTitle_019cd38a-fdd8-7148-a658-16d76486954f" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_TradingSymbol_019cd38a-fdd8-7ea1-ac1a-8fcb8f0c763d" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_TradingSymbol"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_TradingSymbol_019cd38a-fdd8-7ea1-ac1a-8fcb8f0c763d" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_SecurityExchangeName_019cd38a-fdd8-7faa-9be2-1517f502e9e0" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_SecurityExchangeName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_SecurityExchangeName_019cd38a-fdd8-7faa-9be2-1517f502e9e0" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCurrentReportingStatus_019cd38a-fdd8-7296-b5ed-7bafc47b3224" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityCurrentReportingStatus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityCurrentReportingStatus_019cd38a-fdd8-7296-b5ed-7bafc47b3224" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityInteractiveDataCurrent_019cd38a-fdd8-7d60-9ac3-917303c6fa5e" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityInteractiveDataCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityInteractiveDataCurrent_019cd38a-fdd8-7d60-9ac3-917303c6fa5e" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFilerCategory_019cd38a-fdd8-7a0b-b4c9-e3784e16c1a4" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityFilerCategory"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityFilerCategory_019cd38a-fdd8-7a0b-b4c9-e3784e16c1a4" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntitySmallBusiness_019cd38a-fdd8-78f7-886f-b3a62c9c66c4" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntitySmallBusiness"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntitySmallBusiness_019cd38a-fdd8-78f7-886f-b3a62c9c66c4" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityEmergingGrowthCompany_019cd38a-fdd8-73ef-8b9a-4787b7ebcafb" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityEmergingGrowthCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityEmergingGrowthCompany_019cd38a-fdd8-73ef-8b9a-4787b7ebcafb" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityShellCompany_019cd38a-fdd8-77e7-9041-41697ed2534f" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityShellCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityShellCompany_019cd38a-fdd8-77e7-9041-41697ed2534f" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCommonStockSharesOutstanding_019cd38a-fdd8-74a1-b729-41c69cded3ed" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityCommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityCommonStockSharesOutstanding_019cd38a-fdd8-74a1-b729-41c69cded3ed" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCentralIndexKey_019cd38a-fdd8-7604-925e-3a7b4205bad4" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityCentralIndexKey"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_EntityCentralIndexKey_019cd38a-fdd8-7604-925e-3a7b4205bad4" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CurrentFiscalYearEndDate_019cd38a-fdd8-7d16-9933-15e8642becf6" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_CurrentFiscalYearEndDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_CurrentFiscalYearEndDate_019cd38a-fdd8-7d16-9933-15e8642becf6" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentFiscalYearFocus_019cd38a-fdd8-70ea-b4b5-c0a2ee2c46e2" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentFiscalYearFocus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_DocumentFiscalYearFocus_019cd38a-fdd8-70ea-b4b5-c0a2ee2c46e2" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentFiscalPeriodFocus_019cd38a-fdd8-7b83-8ca3-f34a33cbb4eb" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentFiscalPeriodFocus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_DocumentFiscalPeriodFocus_019cd38a-fdd8-7b83-8ca3-f34a33cbb4eb" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AmendmentFlag_019cd38a-fdd8-772d-afb2-7ad60275123b" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_AmendmentFlag"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019cd38a-fdd8-755a-b184-f6c58da84936" xlink:to="loc_dei_AmendmentFlag_019cd38a-fdd8-772d-afb2-7ad60275123b" xlink:type="arc" order="29"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/CondensedConsolidatedBalanceSheetsUnaudited" xlink:type="simple" xlink:href="sdgr-20260331.xsd#CondensedConsolidatedBalanceSheetsUnaudited"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/CondensedConsolidatedBalanceSheetsUnaudited" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019cd38a-fdd8-70d0-8226-86c40facd09c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019cd38a-fdd8-7794-8e5b-5d344142c203" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-70d0-8226-86c40facd09c" xlink:to="loc_us-gaap_StatementTable_019cd38a-fdd8-7794-8e5b-5d344142c203" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-758f-95ef-42a7e9906d3d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019cd38a-fdd8-7794-8e5b-5d344142c203" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-758f-95ef-42a7e9906d3d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-758f-95ef-42a7e9906d3d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-758f-95ef-42a7e9906d3d" xlink:to="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-758f-95ef-42a7e9906d3d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-71bd-bc7d-95eaea9c6d4c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-758f-95ef-42a7e9906d3d" xlink:to="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-71bd-bc7d-95eaea9c6d4c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_UnallocatedCommonStocksMember_019cd38a-fdd8-732a-be96-38ab9dbef08c" xlink:href="sdgr-20260331.xsd#sdgr_UnallocatedCommonStocksMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-71bd-bc7d-95eaea9c6d4c" xlink:to="loc_sdgr_UnallocatedCommonStocksMember_019cd38a-fdd8-732a-be96-38ab9dbef08c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_LimitedCommonStockMember_019cd38a-fdd8-7aa6-9378-d833e57abe7b" xlink:href="sdgr-20260331.xsd#sdgr_LimitedCommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-71bd-bc7d-95eaea9c6d4c" xlink:to="loc_sdgr_LimitedCommonStockMember_019cd38a-fdd8-7aa6-9378-d833e57abe7b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsAbstract_019cd38a-fdd8-7aeb-ab28-f6adaf67c3e8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-70d0-8226-86c40facd09c" xlink:to="loc_us-gaap_AssetsAbstract_019cd38a-fdd8-7aeb-ab28-f6adaf67c3e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrentAbstract_019cd38a-fdd8-79b5-b13f-7d6b3bea7033" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsCurrentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_019cd38a-fdd8-7aeb-ab28-f6adaf67c3e8" xlink:to="loc_us-gaap_AssetsCurrentAbstract_019cd38a-fdd8-79b5-b13f-7d6b3bea7033" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019cd38a-fdd8-72c1-b9e1-1d8aa0c4934a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsCurrentAbstract_019cd38a-fdd8-79b5-b13f-7d6b3bea7033" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_019cd38a-fdd8-72c1-b9e1-1d8aa0c4934a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashCurrent_019cd38a-fdd8-73c5-966a-f352cbc004e2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedCashCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsCurrentAbstract_019cd38a-fdd8-79b5-b13f-7d6b3bea7033" xlink:to="loc_us-gaap_RestrictedCashCurrent_019cd38a-fdd8-73c5-966a-f352cbc004e2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MarketableSecuritiesCurrent_019cd38a-fdd8-7df1-8417-46bc4cd025e9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_MarketableSecuritiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsCurrentAbstract_019cd38a-fdd8-79b5-b13f-7d6b3bea7033" xlink:to="loc_us-gaap_MarketableSecuritiesCurrent_019cd38a-fdd8-7df1-8417-46bc4cd025e9" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_019cd38a-fdd8-7258-8b4f-7f902732ed77" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsCurrentAbstract_019cd38a-fdd8-79b5-b13f-7d6b3bea7033" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_019cd38a-fdd8-7258-8b4f-7f902732ed77" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_UnbilledAndOtherReceivablesCurrent_019cd38a-fdd8-7792-b836-96475b3c1ef6" xlink:href="sdgr-20260331.xsd#sdgr_UnbilledAndOtherReceivablesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsCurrentAbstract_019cd38a-fdd8-79b5-b13f-7d6b3bea7033" xlink:to="loc_sdgr_UnbilledAndOtherReceivablesCurrent_019cd38a-fdd8-7792-b836-96475b3c1ef6" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseCurrent_019cd38a-fdd8-73b6-85a5-7386f6a69658" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PrepaidExpenseCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsCurrentAbstract_019cd38a-fdd8-79b5-b13f-7d6b3bea7033" xlink:to="loc_us-gaap_PrepaidExpenseCurrent_019cd38a-fdd8-73b6-85a5-7386f6a69658" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_019cd38a-fdd8-77eb-943b-29cf885eb7ca" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsCurrentAbstract_019cd38a-fdd8-79b5-b13f-7d6b3bea7033" xlink:to="loc_us-gaap_AssetsCurrent_019cd38a-fdd8-77eb-943b-29cf885eb7ca" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_019cd38a-fdd8-720a-82f8-189abc40381f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_019cd38a-fdd8-7aeb-ab28-f6adaf67c3e8" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_019cd38a-fdd8-720a-82f8-189abc40381f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestments_019cd38a-fdd8-7662-b6fe-1167a18b7d40" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityMethodInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_019cd38a-fdd8-7aeb-ab28-f6adaf67c3e8" xlink:to="loc_us-gaap_EquityMethodInvestments_019cd38a-fdd8-7662-b6fe-1167a18b7d40" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_019cd38a-fdd8-7738-a156-fdb2f3ac3fdb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Goodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_019cd38a-fdd8-7aeb-ab28-f6adaf67c3e8" xlink:to="loc_us-gaap_Goodwill_019cd38a-fdd8-7738-a156-fdb2f3ac3fdb" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_019cd38a-fdd8-7181-a6e9-521fb85b824c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_019cd38a-fdd8-7aeb-ab28-f6adaf67c3e8" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_019cd38a-fdd8-7181-a6e9-521fb85b824c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_019cd38a-fdd8-7659-b86d-bc376e05656f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_019cd38a-fdd8-7aeb-ab28-f6adaf67c3e8" xlink:to="loc_us-gaap_OtherAssetsNoncurrent_019cd38a-fdd8-7659-b86d-bc376e05656f" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_019cd38a-fdd8-7178-9902-27d339c36602" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Assets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract_019cd38a-fdd8-7aeb-ab28-f6adaf67c3e8" xlink:to="loc_us-gaap_Assets_019cd38a-fdd8-7178-9902-27d339c36602" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquityAbstract_019cd38a-fdd8-7c37-b51d-55e6759bcb45" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-70d0-8226-86c40facd09c" xlink:to="loc_us-gaap_LiabilitiesAndStockholdersEquityAbstract_019cd38a-fdd8-7c37-b51d-55e6759bcb45" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrentAbstract_019cd38a-fdd8-71a7-ae1b-aa6531c05210" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LiabilitiesCurrentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquityAbstract_019cd38a-fdd8-7c37-b51d-55e6759bcb45" xlink:to="loc_us-gaap_LiabilitiesCurrentAbstract_019cd38a-fdd8-71a7-ae1b-aa6531c05210" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_019cd38a-fdd8-7050-9254-abee9c1caa5a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesCurrentAbstract_019cd38a-fdd8-71a7-ae1b-aa6531c05210" xlink:to="loc_us-gaap_AccountsPayableCurrent_019cd38a-fdd8-7050-9254-abee9c1caa5a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedPayrollTaxesCurrent_019cd38a-fdd8-7401-ad75-9783d903f8dd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccruedPayrollTaxesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesCurrentAbstract_019cd38a-fdd8-71a7-ae1b-aa6531c05210" xlink:to="loc_us-gaap_AccruedPayrollTaxesCurrent_019cd38a-fdd8-7401-ad75-9783d903f8dd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_019cd38a-fdd8-7998-92bf-1dd9c8e8e661" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesCurrentAbstract_019cd38a-fdd8-71a7-ae1b-aa6531c05210" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_019cd38a-fdd8-7998-92bf-1dd9c8e8e661" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_019cd38a-fdd8-7bb6-8ddf-8883ca9ddbe8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesCurrentAbstract_019cd38a-fdd8-71a7-ae1b-aa6531c05210" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_019cd38a-fdd8-7bb6-8ddf-8883ca9ddbe8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAccruedLiabilitiesCurrent_019cd38a-fdd8-78d9-8ae7-35dd2f3b57de" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherAccruedLiabilitiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesCurrentAbstract_019cd38a-fdd8-71a7-ae1b-aa6531c05210" xlink:to="loc_us-gaap_OtherAccruedLiabilitiesCurrent_019cd38a-fdd8-78d9-8ae7-35dd2f3b57de" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_019cd38a-fdd8-7768-b797-a20e3b108add" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesCurrentAbstract_019cd38a-fdd8-71a7-ae1b-aa6531c05210" xlink:to="loc_us-gaap_LiabilitiesCurrent_019cd38a-fdd8-7768-b797-a20e3b108add" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_019cd38a-fdd8-7a03-884c-52d4a57ae186" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquityAbstract_019cd38a-fdd8-7c37-b51d-55e6759bcb45" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_019cd38a-fdd8-7a03-884c-52d4a57ae186" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_019cd38a-fdd8-74d4-8467-8ee99c110277" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquityAbstract_019cd38a-fdd8-7c37-b51d-55e6759bcb45" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_019cd38a-fdd8-74d4-8467-8ee99c110277" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_019cd38a-fdd8-7445-8d59-3e6678944292" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquityAbstract_019cd38a-fdd8-7c37-b51d-55e6759bcb45" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_019cd38a-fdd8-7445-8d59-3e6678944292" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_019cd38a-fdd8-74da-aac1-8139a003bd72" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Liabilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquityAbstract_019cd38a-fdd8-7c37-b51d-55e6759bcb45" xlink:to="loc_us-gaap_Liabilities_019cd38a-fdd8-74da-aac1-8139a003bd72" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommitmentsAndContingencies_019cd38a-fdd8-7020-977d-3e0b58afae4b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommitmentsAndContingencies"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquityAbstract_019cd38a-fdd8-7c37-b51d-55e6759bcb45" xlink:to="loc_us-gaap_CommitmentsAndContingencies_019cd38a-fdd8-7020-977d-3e0b58afae4b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityAbstract_019cd38a-fdd8-7095-87e0-200ab4902c75" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquityAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquityAbstract_019cd38a-fdd8-7c37-b51d-55e6759bcb45" xlink:to="loc_us-gaap_StockholdersEquityAbstract_019cd38a-fdd8-7095-87e0-200ab4902c75" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockValue_019cd38a-fdd8-7e8f-ab77-c41f556f215c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PreferredStockValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StockholdersEquityAbstract_019cd38a-fdd8-7095-87e0-200ab4902c75" xlink:to="loc_us-gaap_PreferredStockValue_019cd38a-fdd8-7e8f-ab77-c41f556f215c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_019cd38a-fdd8-75ec-8c0e-ca1f3e0db3cb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StockholdersEquityAbstract_019cd38a-fdd8-7095-87e0-200ab4902c75" xlink:to="loc_us-gaap_CommonStockValue_019cd38a-fdd8-75ec-8c0e-ca1f3e0db3cb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalCommonStock_019cd38a-fdd8-7f5e-be13-8572a41d0f36" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdditionalPaidInCapitalCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StockholdersEquityAbstract_019cd38a-fdd8-7095-87e0-200ab4902c75" xlink:to="loc_us-gaap_AdditionalPaidInCapitalCommonStock_019cd38a-fdd8-7f5e-be13-8572a41d0f36" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_019cd38a-fdd8-75f8-9980-87f90d5a6767" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StockholdersEquityAbstract_019cd38a-fdd8-7095-87e0-200ab4902c75" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_019cd38a-fdd8-75f8-9980-87f90d5a6767" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_019cd38a-fdd8-730a-8d87-04fad56b6ac1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StockholdersEquityAbstract_019cd38a-fdd8-7095-87e0-200ab4902c75" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_019cd38a-fdd8-730a-8d87-04fad56b6ac1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019cd38a-fdd8-72be-b586-65c8dc38a8bf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StockholdersEquityAbstract_019cd38a-fdd8-7095-87e0-200ab4902c75" xlink:to="loc_us-gaap_StockholdersEquity_019cd38a-fdd8-72be-b586-65c8dc38a8bf" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_019cd38a-fdd8-75e0-93c8-8fd1f02f3fcd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquityAbstract_019cd38a-fdd8-7c37-b51d-55e6759bcb45" xlink:to="loc_us-gaap_LiabilitiesAndStockholdersEquity_019cd38a-fdd8-75e0-93c8-8fd1f02f3fcd" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical" xlink:type="simple" xlink:href="sdgr-20260331.xsd#CondensedConsolidatedBalanceSheetsUnauditedParenthetical"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/CondensedConsolidatedBalanceSheetsUnauditedParenthetical" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019cd38a-fdd8-72aa-a812-f12f3cdfe5e4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_StatementTable_019cd38a-fdd8-72aa-a812-f12f3cdfe5e4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-7321-a42e-a767723608e8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019cd38a-fdd8-72aa-a812-f12f3cdfe5e4" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-7321-a42e-a767723608e8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-7321-a42e-a767723608e8_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-7321-a42e-a767723608e8" xlink:to="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-7321-a42e-a767723608e8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-7fc3-87a0-7b5a56cb1052" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd8-7321-a42e-a767723608e8" xlink:to="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-7fc3-87a0-7b5a56cb1052" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_UnallocatedCommonStocksMember_019cd38a-fdd8-7be0-87de-3cc01c5fe70d" xlink:href="sdgr-20260331.xsd#sdgr_UnallocatedCommonStocksMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-7fc3-87a0-7b5a56cb1052" xlink:to="loc_sdgr_UnallocatedCommonStocksMember_019cd38a-fdd8-7be0-87de-3cc01c5fe70d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_LimitedCommonStockMember_019cd38a-fdd8-79f4-9978-6b485a01c396" xlink:href="sdgr-20260331.xsd#sdgr_LimitedCommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd8-7fc3-87a0-7b5a56cb1052" xlink:to="loc_sdgr_LimitedCommonStockMember_019cd38a-fdd8-79f4-9978-6b485a01c396" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc0f-2e33-7cac-aee1-b0e56a7c6553" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019cd38a-fdd8-72aa-a812-f12f3cdfe5e4" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc0f-2e33-7cac-aee1-b0e56a7c6553" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019ddc0f-2e33-7cac-aee1-b0e56a7c6553_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc0f-2e33-7cac-aee1-b0e56a7c6553" xlink:to="loc_us-gaap_RelatedPartyDomain_019ddc0f-2e33-7cac-aee1-b0e56a7c6553_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019ddc0f-2e33-7eaa-b297-bdd3481508fb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc0f-2e33-7cac-aee1-b0e56a7c6553" xlink:to="loc_us-gaap_RelatedPartyDomain_019ddc0f-2e33-7eaa-b297-bdd3481508fb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyMember_019ddc0f-2e33-76d1-b164-de295a7311c6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_019ddc0f-2e33-7eaa-b297-bdd3481508fb" xlink:to="loc_us-gaap_RelatedPartyMember_019ddc0f-2e33-76d1-b164-de295a7311c6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashCurrent_019ddc0f-2e33-75c9-a9fb-e3b43af44c1e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedCashCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_RestrictedCashCurrent_019ddc0f-2e33-75c9-a9fb-e3b43af44c1e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableCurrent_019cd38a-fdd8-79df-9467-532b71b3a172" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AllowanceForDoubtfulAccountsReceivableCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_AllowanceForDoubtfulAccountsReceivableCurrent_019cd38a-fdd8-79df-9467-532b71b3a172" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_AllowanceForUnbilledReceivablesCurrent_019cd38a-fdd8-744c-8028-69cd55ed4fb5" xlink:href="sdgr-20260331.xsd#sdgr_AllowanceForUnbilledReceivablesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_sdgr_AllowanceForUnbilledReceivablesCurrent_019cd38a-fdd8-744c-8028-69cd55ed4fb5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019cd38a-fdd8-778e-967e-f94f6f8c6a35" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PreferredStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019cd38a-fdd8-778e-967e-f94f6f8c6a35" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesAuthorized_019cd38a-fdd8-75f4-bbb1-4035097c16e1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PreferredStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_PreferredStockSharesAuthorized_019cd38a-fdd8-75f4-bbb1-4035097c16e1" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesIssued_019cd38a-fdd8-7662-927d-a4142abab289" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PreferredStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_PreferredStockSharesIssued_019cd38a-fdd8-7662-927d-a4142abab289" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesOutstanding_019cd38a-fdd8-76f1-b89d-c37bca70bb70" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PreferredStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_PreferredStockSharesOutstanding_019cd38a-fdd8-76f1-b89d-c37bca70bb70" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_019cd38a-fdd8-748c-97a9-9cd206b94319" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_019cd38a-fdd8-748c-97a9-9cd206b94319" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesAuthorized_019cd38a-fdd8-77e1-8408-ce0c8e196857" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_CommonStockSharesAuthorized_019cd38a-fdd8-77e1-8408-ce0c8e196857" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesIssued_019cd38a-fdd8-7fd9-bcc8-67ce731be89e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_CommonStockSharesIssued_019cd38a-fdd8-7fd9-bcc8-67ce731be89e" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_019cd38a-fdd8-7eb8-9172-41f9abec170f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7060-8588-b3f1b87ed178" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_019cd38a-fdd8-7eb8-9172-41f9abec170f" xlink:type="arc" order="10"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/CondensedConsolidatedStatementsofOperationsUnaudited" xlink:type="simple" xlink:href="sdgr-20260331.xsd#CondensedConsolidatedStatementsofOperationsUnaudited"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/CondensedConsolidatedStatementsofOperationsUnaudited" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019cd38a-fdd8-7465-ae47-6c7c00f73897" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_StatementTable_019cd38a-fdd8-7465-ae47-6c7c00f73897" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7ab6-845c-04e368abd6e7" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019cd38a-fdd8-7465-ae47-6c7c00f73897" xlink:to="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7ab6-845c-04e368abd6e7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7ab6-845c-04e368abd6e7_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7ab6-845c-04e368abd6e7" xlink:to="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7ab6-845c-04e368abd6e7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-73f9-aea7-3a66f393e404" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7ab6-845c-04e368abd6e7" xlink:to="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-73f9-aea7-3a66f393e404" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareProductsAndServicesMember_019cd38a-fdd8-7f8f-97b6-e6d1dc8f3aac" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareProductsAndServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-73f9-aea7-3a66f393e404" xlink:to="loc_sdgr_SoftwareProductsAndServicesMember_019cd38a-fdd8-7f8f-97b6-e6d1dc8f3aac" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoveryMember_019cd38a-fdd8-7728-8815-f35fb8fc1f24" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoveryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-73f9-aea7-3a66f393e404" xlink:to="loc_sdgr_DrugDiscoveryMember_019cd38a-fdd8-7728-8815-f35fb8fc1f24" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContributionMember_019d76d4-b471-7b97-ad98-901620d1c27b" xlink:href="sdgr-20260331.xsd#sdgr_ContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-73f9-aea7-3a66f393e404" xlink:to="loc_sdgr_ContributionMember_019d76d4-b471-7b97-ad98-901620d1c27b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_019cd38a-fdd8-7009-a63c-e79530a43a45" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenuesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_RevenuesAbstract_019cd38a-fdd8-7009-a63c-e79530a43a45" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_019cd38a-fdd8-7ef7-8c26-5a17103da482" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_019cd38a-fdd8-7009-a63c-e79530a43a45" xlink:to="loc_us-gaap_Revenues_019cd38a-fdd8-7ef7-8c26-5a17103da482" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfRevenueAbstract_019cd38a-fdd8-75ed-9ebc-dec6249a541f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostOfRevenueAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_CostOfRevenueAbstract_019cd38a-fdd8-75ed-9ebc-dec6249a541f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfRevenue_019cd38a-fdd8-75ba-8e9e-3c8b392a548f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostOfRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostOfRevenueAbstract_019cd38a-fdd8-75ed-9ebc-dec6249a541f" xlink:to="loc_us-gaap_CostOfRevenue_019cd38a-fdd8-75ba-8e9e-3c8b392a548f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GrossProfit_019cd38a-fdd8-7d15-a13f-226a6e3ae1f9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GrossProfit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_GrossProfit_019cd38a-fdd8-7d15-a13f-226a6e3ae1f9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpensesAbstract_019cd38a-fdd8-7ec4-97ab-b05e30431365" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_OperatingExpensesAbstract_019cd38a-fdd8-7ec4-97ab-b05e30431365" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_019cd38a-fdd8-7151-8a40-d60513079129" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_019cd38a-fdd8-7ec4-97ab-b05e30431365" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_019cd38a-fdd8-7151-8a40-d60513079129" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingAndMarketingExpense_019cd38a-fdd8-779c-95f5-d40cedda30d5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SellingAndMarketingExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_019cd38a-fdd8-7ec4-97ab-b05e30431365" xlink:to="loc_us-gaap_SellingAndMarketingExpense_019cd38a-fdd8-779c-95f5-d40cedda30d5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_019cd38a-fdd8-780d-bbb8-08fc55883b4a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_019cd38a-fdd8-7ec4-97ab-b05e30431365" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_019cd38a-fdd8-780d-bbb8-08fc55883b4a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_019cd38a-fdd8-7bb7-a8da-7b81b7afb3b6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_019cd38a-fdd8-7ec4-97ab-b05e30431365" xlink:to="loc_us-gaap_OperatingExpenses_019cd38a-fdd8-7bb7-a8da-7b81b7afb3b6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_019cd38a-fdd8-7ac1-b2fd-bf980189cbff" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_OperatingIncomeLoss_019cd38a-fdd8-7ac1-b2fd-bf980189cbff" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpenseAbstract_019cd38a-fdd8-7163-aa4f-7acc6953748b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NonoperatingIncomeExpenseAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_NonoperatingIncomeExpenseAbstract_019cd38a-fdd8-7163-aa4f-7acc6953748b" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNiGainLoss_019cd38a-fdd8-7115-8273-6860bcbfdc6d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquitySecuritiesFvNiGainLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NonoperatingIncomeExpenseAbstract_019cd38a-fdd8-7163-aa4f-7acc6953748b" xlink:to="loc_us-gaap_EquitySecuritiesFvNiGainLoss_019cd38a-fdd8-7115-8273-6860bcbfdc6d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_019cd38a-fdd8-7f0d-b41a-bd88c37f936d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NonoperatingIncomeExpenseAbstract_019cd38a-fdd8-7163-aa4f-7acc6953748b" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_019cd38a-fdd8-7f0d-b41a-bd88c37f936d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_019cd38a-fdd8-78f7-8509-829fa34d2b45" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NonoperatingIncomeExpenseAbstract_019cd38a-fdd8-7163-aa4f-7acc6953748b" xlink:to="loc_us-gaap_NonoperatingIncomeExpense_019cd38a-fdd8-78f7-8509-829fa34d2b45" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019cd38a-fdd8-7a6a-b065-cbd111e1963a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_019cd38a-fdd8-7a6a-b065-cbd111e1963a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_019cd38a-fdd8-7a95-9a0d-d808cb0b9e87" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_019cd38a-fdd8-7a95-9a0d-d808cb0b9e87" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019cd38a-fdd8-7b59-80ee-d36932c1bbbc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_NetIncomeLoss_019cd38a-fdd8-7b59-80ee-d36932c1bbbc" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_019cd38a-fdd8-793b-bf36-707d466aaaa9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_EarningsPerShareBasic_019cd38a-fdd8-793b-bf36-707d466aaaa9" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_019cd38a-fdd8-78ce-ab28-ad40a1319145" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_EarningsPerShareDiluted_019cd38a-fdd8-78ce-ab28-ad40a1319145" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_019cd38a-fdd8-7492-afe2-42deb2a7fe50" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_019cd38a-fdd8-7492-afe2-42deb2a7fe50" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019cd38a-fdd8-7aac-a730-b620b9c97538" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7a8f-824b-3e49185479f5" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_019cd38a-fdd8-7aac-a730-b620b9c97538" xlink:type="arc" order="12"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/CondensedConsolidatedStatementsofOperationsUnauditedParenthetical" xlink:type="simple" xlink:href="sdgr-20260331.xsd#CondensedConsolidatedStatementsofOperationsUnauditedParenthetical"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/CondensedConsolidatedStatementsofOperationsUnauditedParenthetical" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019ddc15-8beb-7d48-8e58-59c43c896d16" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019ddc15-8beb-7d15-aef5-4485b753d723" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019ddc15-8beb-7d48-8e58-59c43c896d16" xlink:to="loc_us-gaap_StatementTable_019ddc15-8beb-7d15-aef5-4485b753d723" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019ddc15-8beb-7368-9873-9199e99cef07" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019ddc15-8beb-7d15-aef5-4485b753d723" xlink:to="loc_srt_ProductOrServiceAxis_019ddc15-8beb-7368-9873-9199e99cef07" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ddc15-8beb-7368-9873-9199e99cef07_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019ddc15-8beb-7368-9873-9199e99cef07" xlink:to="loc_srt_ProductsAndServicesDomain_019ddc15-8beb-7368-9873-9199e99cef07_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019ddc15-8beb-7103-b0ff-2cad82e6a243" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019ddc15-8beb-7368-9873-9199e99cef07" xlink:to="loc_srt_ProductsAndServicesDomain_019ddc15-8beb-7103-b0ff-2cad82e6a243" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareProductsAndServicesMember_019ddc15-8beb-7eb0-bf21-42f3799d6f5f" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareProductsAndServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ddc15-8beb-7103-b0ff-2cad82e6a243" xlink:to="loc_sdgr_SoftwareProductsAndServicesMember_019ddc15-8beb-7eb0-bf21-42f3799d6f5f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContributionMember_019ddc16-2efe-7803-b48f-0fece84023ab" xlink:href="sdgr-20260331.xsd#sdgr_ContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019ddc15-8beb-7103-b0ff-2cad82e6a243" xlink:to="loc_sdgr_ContributionMember_019ddc16-2efe-7803-b48f-0fece84023ab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc15-8beb-7eb0-aede-bc3913e7d44d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019ddc15-8beb-7d15-aef5-4485b753d723" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc15-8beb-7eb0-aede-bc3913e7d44d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019ddc15-8beb-7eb0-aede-bc3913e7d44d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc15-8beb-7eb0-aede-bc3913e7d44d" xlink:to="loc_us-gaap_RelatedPartyDomain_019ddc15-8beb-7eb0-aede-bc3913e7d44d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019ddc15-8beb-71dc-89af-e193a07b5b94" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc15-8beb-7eb0-aede-bc3913e7d44d" xlink:to="loc_us-gaap_RelatedPartyDomain_019ddc15-8beb-71dc-89af-e193a07b5b94" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyMember_019ddc15-8beb-7525-888a-881ddcee25ab" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_019ddc15-8beb-71dc-89af-e193a07b5b94" xlink:to="loc_us-gaap_RelatedPartyMember_019ddc15-8beb-7525-888a-881ddcee25ab" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_DirectorMember_019ddc17-40ff-7324-a0e6-06c40310c751" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_DirectorMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_019ddc15-8beb-71dc-89af-e193a07b5b94" xlink:to="loc_srt_DirectorMember_019ddc17-40ff-7324-a0e6-06c40310c751" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_019ddc15-8beb-797b-8421-f2fca8832fcd" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019ddc15-8beb-7d48-8e58-59c43c896d16" xlink:to="loc_us-gaap_Revenues_019ddc15-8beb-797b-8421-f2fca8832fcd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_019ddc16-9023-7fa3-89ae-db595ed86543" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019ddc15-8beb-7d48-8e58-59c43c896d16" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_019ddc16-9023-7fa3-89ae-db595ed86543" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionAmountsOfTransaction_019ddc17-40ff-7ae9-8386-15a7c7c7c76e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyTransactionAmountsOfTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019ddc15-8beb-7d48-8e58-59c43c896d16" xlink:to="loc_us-gaap_RelatedPartyTransactionAmountsOfTransaction_019ddc17-40ff-7ae9-8386-15a7c7c7c76e" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/CondensedConsolidatedStatementsofStockholdersEquityUnaudited" xlink:type="simple" xlink:href="sdgr-20260331.xsd#CondensedConsolidatedStatementsofStockholdersEquityUnaudited"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/CondensedConsolidatedStatementsofStockholdersEquityUnaudited" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7c1a-a96c-f9843dc15401" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019cd38a-fdd8-791d-9c6f-dab0928a2ce9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7c1a-a96c-f9843dc15401" xlink:to="loc_us-gaap_StatementTable_019cd38a-fdd8-791d-9c6f-dab0928a2ce9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_019cd38a-fdd8-7ba0-afb0-eb19c6a84244" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019cd38a-fdd8-791d-9c6f-dab0928a2ce9" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_019cd38a-fdd8-7ba0-afb0-eb19c6a84244" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019cd38a-fdd8-7ba0-afb0-eb19c6a84244_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019cd38a-fdd8-7ba0-afb0-eb19c6a84244" xlink:to="loc_us-gaap_EquityComponentDomain_019cd38a-fdd8-7ba0-afb0-eb19c6a84244_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019cd38a-fdd8-7252-950c-a51e569ff07b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019cd38a-fdd8-7ba0-afb0-eb19c6a84244" xlink:to="loc_us-gaap_EquityComponentDomain_019cd38a-fdd8-7252-950c-a51e569ff07b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_019cd38a-fdd8-73d7-95c8-b433e8fabe1a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019cd38a-fdd8-7252-950c-a51e569ff07b" xlink:to="loc_us-gaap_CommonStockMember_019cd38a-fdd8-73d7-95c8-b433e8fabe1a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_LimitedCommonStockMember_019cd38a-fdd8-7c2b-8572-f133ce8923ea" xlink:href="sdgr-20260331.xsd#sdgr_LimitedCommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019cd38a-fdd8-7252-950c-a51e569ff07b" xlink:to="loc_sdgr_LimitedCommonStockMember_019cd38a-fdd8-7c2b-8572-f133ce8923ea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_019cd38a-fdd8-7298-be9b-93a6ac9a33f9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019cd38a-fdd8-7252-950c-a51e569ff07b" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_019cd38a-fdd8-7298-be9b-93a6ac9a33f9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_019cd38a-fdd8-7692-a8e7-2416927fc8cc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019cd38a-fdd8-7252-950c-a51e569ff07b" xlink:to="loc_us-gaap_RetainedEarningsMember_019cd38a-fdd8-7692-a8e7-2416927fc8cc" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019cd38a-fdd8-7796-ad09-2fd7acffba71" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019cd38a-fdd8-7252-950c-a51e569ff07b" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019cd38a-fdd8-7796-ad09-2fd7acffba71" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019cd38a-fdd8-7c1a-a96c-f9843dc15401" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_019cd38a-fdd8-7fa7-b608-0954126b647f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:to="loc_us-gaap_SharesOutstanding_019cd38a-fdd8-7fa7-b608-0954126b647f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019cd38a-fdd8-77ce-bb2b-85d284b62d0d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:to="loc_us-gaap_StockholdersEquity_019cd38a-fdd8-77ce-bb2b-85d284b62d0d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_019cd38a-fdd8-71ed-b9c7-0c7405fd13ad" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_019cd38a-fdd8-71ed-b9c7-0c7405fd13ad" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019cd38a-fdd8-7618-9921-d3f5f57046e6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019cd38a-fdd8-7618-9921-d3f5f57046e6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_019cd38a-fdd8-72de-b9b0-77a481c99818" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_019cd38a-fdd8-72de-b9b0-77a481c99818" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures_019cd38a-fdd8-7842-aa71-cf8696f36bdf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures_019cd38a-fdd8-7842-aa71-cf8696f36bdf" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardNetOfForfeitures_019cd38a-fdd8-7e71-907a-e233446d08a4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardNetOfForfeitures"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardNetOfForfeitures_019cd38a-fdd8-7e71-907a-e233446d08a4" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_019cd38a-fdd8-7c48-bb80-493fcb80663c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_019cd38a-fdd8-7c48-bb80-493fcb80663c" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProfitLoss_019cd38a-fdd8-7691-bf7c-bebc6b7cc4c9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProfitLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019cd38a-fdd8-775d-8514-6f7fd015e655" xlink:to="loc_us-gaap_ProfitLoss_019cd38a-fdd8-7691-bf7c-bebc6b7cc4c9" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_019cd38a-fdd8-7212-ac6b-2d3ebf6317a2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019cd38a-fdd8-7c76-9e7f-907664b05f7c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/CondensedConsolidatedStatementsofCashFlowsUnauditedParenthetical" xlink:type="simple" xlink:href="sdgr-20260331.xsd#CondensedConsolidatedStatementsofCashFlowsUnauditedParenthetical"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/CondensedConsolidatedStatementsofCashFlowsUnauditedParenthetical" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019ddc1a-f158-72a7-bdbd-c2c1547c9dc3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019ddc1a-f158-72e5-8a93-2b7d93a481d6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019ddc1a-f158-72a7-bdbd-c2c1547c9dc3" xlink:to="loc_us-gaap_StatementTable_019ddc1a-f158-72e5-8a93-2b7d93a481d6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc1a-f158-78b3-bb0a-c81d1496a6ca" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019ddc1a-f158-72e5-8a93-2b7d93a481d6" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc1a-f158-78b3-bb0a-c81d1496a6ca" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019ddc1a-f158-78b3-bb0a-c81d1496a6ca_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc1a-f158-78b3-bb0a-c81d1496a6ca" xlink:to="loc_us-gaap_RelatedPartyDomain_019ddc1a-f158-78b3-bb0a-c81d1496a6ca_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019ddc1a-f158-77bb-8d9d-d20778f908c9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019ddc1a-f158-78b3-bb0a-c81d1496a6ca" xlink:to="loc_us-gaap_RelatedPartyDomain_019ddc1a-f158-77bb-8d9d-d20778f908c9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyMember_019ddc1a-f158-7ea8-a217-96eef2528c17" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_019ddc1a-f158-77bb-8d9d-d20778f908c9" xlink:to="loc_us-gaap_RelatedPartyMember_019ddc1a-f158-7ea8-a217-96eef2528c17" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_019ddc1a-f158-722e-8cfc-b63158afb49c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019ddc1a-f158-72a7-bdbd-c2c1547c9dc3" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_019ddc1a-f158-722e-8cfc-b63158afb49c" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/SignificantAccountingPoliciesDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#SignificantAccountingPoliciesDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/SignificantAccountingPoliciesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SignificantAccountingPoliciesLineItems_019cd38a-fdd8-780d-b51a-5025e2ee5f7f" xlink:href="sdgr-20260331.xsd#sdgr_SignificantAccountingPoliciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SignificantAccountingPoliciesTable_019cd38a-fdd8-797d-a7a4-84d98ce8e7ef" xlink:href="sdgr-20260331.xsd#sdgr_SignificantAccountingPoliciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_sdgr_SignificantAccountingPoliciesLineItems_019cd38a-fdd8-780d-b51a-5025e2ee5f7f" xlink:to="loc_sdgr_SignificantAccountingPoliciesTable_019cd38a-fdd8-797d-a7a4-84d98ce8e7ef" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_019cd38a-fdd8-774a-a179-16f61981a693" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_sdgr_SignificantAccountingPoliciesTable_019cd38a-fdd8-797d-a7a4-84d98ce8e7ef" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_019cd38a-fdd8-774a-a179-16f61981a693" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_019cd38a-fdd8-774a-a179-16f61981a693_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_019cd38a-fdd8-774a-a179-16f61981a693" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_019cd38a-fdd8-774a-a179-16f61981a693_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_019cd38a-fdd8-7784-addb-431d98ddd877" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_019cd38a-fdd8-774a-a179-16f61981a693" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_019cd38a-fdd8-7784-addb-431d98ddd877" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_019cd38a-fdd8-7d8e-ba10-1b82779a1999" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CustomerConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_019cd38a-fdd8-7784-addb-431d98ddd877" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_019cd38a-fdd8-7d8e-ba10-1b82779a1999" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019cd38a-fdd8-730c-ae03-e97b54ec7b94" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_sdgr_SignificantAccountingPoliciesTable_019cd38a-fdd8-797d-a7a4-84d98ce8e7ef" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019cd38a-fdd8-730c-ae03-e97b54ec7b94" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cd38a-fdd8-730c-ae03-e97b54ec7b94_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019cd38a-fdd8-730c-ae03-e97b54ec7b94" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cd38a-fdd8-730c-ae03-e97b54ec7b94_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cd38a-fdd8-721b-8596-178a6f3acda0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_019cd38a-fdd8-730c-ae03-e97b54ec7b94" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cd38a-fdd8-721b-8596-178a6f3acda0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableMember_019cd38a-fdd8-7805-9485-3248acfe0ccb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cd38a-fdd8-721b-8596-178a6f3acda0" xlink:to="loc_us-gaap_AccountsReceivableMember_019cd38a-fdd8-7805-9485-3248acfe0ccb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContractAssetsMember_019cd38a-fdd8-79a9-a9cd-8c2e68728efe" xlink:href="sdgr-20260331.xsd#sdgr_ContractAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cd38a-fdd8-721b-8596-178a6f3acda0" xlink:to="loc_sdgr_ContractAssetsMember_019cd38a-fdd8-79a9-a9cd-8c2e68728efe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SalesRevenueNetMember_019cd38a-fdd8-7e0d-a990-b9c23d5faf8e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SalesRevenueNetMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_019cd38a-fdd8-721b-8596-178a6f3acda0" xlink:to="loc_us-gaap_SalesRevenueNetMember_019cd38a-fdd8-7e0d-a990-b9c23d5faf8e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_019cd38a-fdd8-7db5-87a2-76803d2ade20" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_sdgr_SignificantAccountingPoliciesTable_019cd38a-fdd8-797d-a7a4-84d98ce8e7ef" xlink:to="loc_srt_MajorCustomersAxis_019cd38a-fdd8-7db5-87a2-76803d2ade20" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_019cd38a-fdd8-7db5-87a2-76803d2ade20_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_019cd38a-fdd8-7db5-87a2-76803d2ade20" xlink:to="loc_srt_NameOfMajorCustomerDomain_019cd38a-fdd8-7db5-87a2-76803d2ade20_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_019cd38a-fdd8-7486-a829-420ffbbb7bfe" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_019cd38a-fdd8-7db5-87a2-76803d2ade20" xlink:to="loc_srt_NameOfMajorCustomerDomain_019cd38a-fdd8-7486-a829-420ffbbb7bfe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_CustomerAMember_019cd38a-fdd8-7b00-87d3-f630411e0e30" xlink:href="sdgr-20260331.xsd#sdgr_CustomerAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019cd38a-fdd8-7486-a829-420ffbbb7bfe" xlink:to="loc_sdgr_CustomerAMember_019cd38a-fdd8-7b00-87d3-f630411e0e30" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_CustomerBMember_019cd38a-fdd8-79fa-9258-b424cd70ab03" xlink:href="sdgr-20260331.xsd#sdgr_CustomerBMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019cd38a-fdd8-7486-a829-420ffbbb7bfe" xlink:to="loc_sdgr_CustomerBMember_019cd38a-fdd8-79fa-9258-b424cd70ab03" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_CustomerCMember_019cd38a-fdd8-77e4-87fe-adeaf2f359a7" xlink:href="sdgr-20260331.xsd#sdgr_CustomerCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_019cd38a-fdd8-7486-a829-420ffbbb7bfe" xlink:to="loc_sdgr_CustomerCMember_019cd38a-fdd8-77e4-87fe-adeaf2f359a7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_019cd38a-fdd8-707e-8aea-592f3f75c6a9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_sdgr_SignificantAccountingPoliciesLineItems_019cd38a-fdd8-780d-b51a-5025e2ee5f7f" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_019cd38a-fdd8-707e-8aea-592f3f75c6a9" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionScheduleofTimingofRevenueRecognitionDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionScheduleofTimingofRevenueRecognitionDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionScheduleofTimingofRevenueRecognitionDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-7cf4-b9d8-fb953c24209a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7bc6-b744-7d16a7101f1b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-7cf4-b9d8-fb953c24209a" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7bc6-b744-7d16a7101f1b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-752c-b1bc-ccd88379340b" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7bc6-b744-7d16a7101f1b" xlink:to="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-752c-b1bc-ccd88379340b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-752c-b1bc-ccd88379340b_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-752c-b1bc-ccd88379340b" xlink:to="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-752c-b1bc-ccd88379340b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7be7-9de0-24f6049e606d" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-752c-b1bc-ccd88379340b" xlink:to="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7be7-9de0-24f6049e606d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareProductsAndServicesMember_019cd38a-fdd8-785a-9c4b-d5050fd45820" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareProductsAndServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7be7-9de0-24f6049e606d" xlink:to="loc_sdgr_SoftwareProductsAndServicesMember_019cd38a-fdd8-785a-9c4b-d5050fd45820" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoveryMember_019cd38a-fdd8-78d4-bdfe-ca53e524f1b3" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoveryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7be7-9de0-24f6049e606d" xlink:to="loc_sdgr_DrugDiscoveryMember_019cd38a-fdd8-78d4-bdfe-ca53e524f1b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContributionMember_019d76de-bb06-77b1-b780-42109221530f" xlink:href="sdgr-20260331.xsd#sdgr_ContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7be7-9de0-24f6049e606d" xlink:to="loc_sdgr_ContributionMember_019d76de-bb06-77b1-b780-42109221530f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TimingOfTransferOfGoodOrServiceAxis_019cd38a-fdd8-773d-8b7e-640fbf93c081" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TimingOfTransferOfGoodOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7bc6-b744-7d16a7101f1b" xlink:to="loc_us-gaap_TimingOfTransferOfGoodOrServiceAxis_019cd38a-fdd8-773d-8b7e-640fbf93c081" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_019cd38a-fdd8-773d-8b7e-640fbf93c081_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TimingOfTransferOfGoodOrServiceDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TimingOfTransferOfGoodOrServiceAxis_019cd38a-fdd8-773d-8b7e-640fbf93c081" xlink:to="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_019cd38a-fdd8-773d-8b7e-640fbf93c081_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_019cd38a-fdd8-767f-9a32-4eab184cdbc5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TimingOfTransferOfGoodOrServiceDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TimingOfTransferOfGoodOrServiceAxis_019cd38a-fdd8-773d-8b7e-640fbf93c081" xlink:to="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_019cd38a-fdd8-767f-9a32-4eab184cdbc5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransferredAtPointInTimeMember_019cd38a-fdd8-7e5e-adb2-a0337f08ac2b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransferredAtPointInTimeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_019cd38a-fdd8-767f-9a32-4eab184cdbc5" xlink:to="loc_us-gaap_TransferredAtPointInTimeMember_019cd38a-fdd8-7e5e-adb2-a0337f08ac2b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransferredOverTimeMember_019cd38a-fdd8-7366-89f4-d8cb72a914e2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransferredOverTimeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TimingOfTransferOfGoodOrServiceDomain_019cd38a-fdd8-767f-9a32-4eab184cdbc5" xlink:to="loc_us-gaap_TransferredOverTimeMember_019cd38a-fdd8-7366-89f4-d8cb72a914e2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_TimingOfRevenueRecognitionPercentage_019cd38a-fdd8-786f-8188-1e34b30860aa" xlink:href="sdgr-20260331.xsd#sdgr_TimingOfRevenueRecognitionPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-7cf4-b9d8-fb953c24209a" xlink:to="loc_sdgr_TimingOfRevenueRecognitionPercentage_019cd38a-fdd8-786f-8188-1e34b30860aa" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionSoftwareProductsandServicesDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionSoftwareProductsandServicesDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionSoftwareProductsandServicesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fc-9750-7cae-8a6a-a63f6c6e74d4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-730a-a004-0ae3d924f38a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fc-9750-7cae-8a6a-a63f6c6e74d4" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-730a-a004-0ae3d924f38a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019d76fc-9750-7595-a13d-d03d52047fa8" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-730a-a004-0ae3d924f38a" xlink:to="loc_srt_ProductOrServiceAxis_019d76fc-9750-7595-a13d-d03d52047fa8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019d76fc-9750-7595-a13d-d03d52047fa8_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019d76fc-9750-7595-a13d-d03d52047fa8" xlink:to="loc_srt_ProductsAndServicesDomain_019d76fc-9750-7595-a13d-d03d52047fa8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019d76fc-9750-78f5-a701-0628780e6367" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019d76fc-9750-7595-a13d-d03d52047fa8" xlink:to="loc_srt_ProductsAndServicesDomain_019d76fc-9750-78f5-a701-0628780e6367" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_OnPremiseSoftwareMember_019d76fc-9750-7076-b01d-af8a498d2943" xlink:href="sdgr-20260331.xsd#sdgr_OnPremiseSoftwareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019d76fc-9750-78f5-a701-0628780e6367" xlink:to="loc_sdgr_OnPremiseSoftwareMember_019d76fc-9750-7076-b01d-af8a498d2943" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_HostedSoftwareMember_019d76fc-9750-7a11-a72e-a18b6e157e6b" xlink:href="sdgr-20260331.xsd#sdgr_HostedSoftwareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019d76fc-9750-78f5-a701-0628780e6367" xlink:to="loc_sdgr_HostedSoftwareMember_019d76fc-9750-7a11-a72e-a18b6e157e6b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RevenueArrangementsContractTerm_019d76fc-9750-751c-9216-380ba3ac06e1" xlink:href="sdgr-20260331.xsd#sdgr_RevenueArrangementsContractTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fc-9750-7cae-8a6a-a63f6c6e74d4" xlink:to="loc_sdgr_RevenueArrangementsContractTerm_019d76fc-9750-751c-9216-380ba3ac06e1" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionScheduleofRevenueRecognizedfromtheSourcesofSoftwareProductsandServicesRevenueDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionScheduleofRevenueRecognizedfromtheSourcesofSoftwareProductsandServicesRevenueDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionScheduleofRevenueRecognizedfromtheSourcesofSoftwareProductsandServicesRevenueDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-7fec-b94d-cffec93c5eee" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7404-a309-5e00e78c3d5f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-7fec-b94d-cffec93c5eee" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7404-a309-5e00e78c3d5f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7c01-ac79-9b66100afda4" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7404-a309-5e00e78c3d5f" xlink:to="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7c01-ac79-9b66100afda4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7c01-ac79-9b66100afda4_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7c01-ac79-9b66100afda4" xlink:to="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7c01-ac79-9b66100afda4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7c2f-ab9d-d033ad9515fa" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7c01-ac79-9b66100afda4" xlink:to="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7c2f-ab9d-d033ad9515fa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_OnPremiseSoftwareMember_019cd38a-fdd8-72dc-9ad2-74cab9255d04" xlink:href="sdgr-20260331.xsd#sdgr_OnPremiseSoftwareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7c2f-ab9d-d033ad9515fa" xlink:to="loc_sdgr_OnPremiseSoftwareMember_019cd38a-fdd8-72dc-9ad2-74cab9255d04" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_HostedSoftwareMember_019cd38a-fdd8-70c4-8f2b-c72977c834c0" xlink:href="sdgr-20260331.xsd#sdgr_HostedSoftwareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7c2f-ab9d-d033ad9515fa" xlink:to="loc_sdgr_HostedSoftwareMember_019cd38a-fdd8-70c4-8f2b-c72977c834c0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MaintenanceMember_019cd38a-fdd8-7e86-bf7e-611666ef35f8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_MaintenanceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7c2f-ab9d-d033ad9515fa" xlink:to="loc_us-gaap_MaintenanceMember_019cd38a-fdd8-7e86-bf7e-611666ef35f8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ProfessionalServicesMember_019cd38a-fdd8-7ed4-a3bf-e3dc3e6d69b6" xlink:href="sdgr-20260331.xsd#sdgr_ProfessionalServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7c2f-ab9d-d033ad9515fa" xlink:to="loc_sdgr_ProfessionalServicesMember_019cd38a-fdd8-7ed4-a3bf-e3dc3e6d69b6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareProductsAndServicesMember_019d76e4-0645-7a15-959e-c760eba2c2cc" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareProductsAndServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7c2f-ab9d-d033ad9515fa" xlink:to="loc_sdgr_SoftwareProductsAndServicesMember_019d76e4-0645-7a15-959e-c760eba2c2cc" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_019d76e6-3c0e-7f2d-917a-5a587762db03" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-7fec-b94d-cffec93c5eee" xlink:to="loc_us-gaap_Revenues_019d76e6-3c0e-7f2d-917a-5a587762db03" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionDrugDiscoveryDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionDrugDiscoveryDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionDrugDiscoveryDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fd-5fc1-7e23-8ab0-d0128e4823c0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7084-a062-584f7cab61bf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fd-5fc1-7e23-8ab0-d0128e4823c0" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7084-a062-584f7cab61bf" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019d76fd-5fc1-7201-9450-18b08e6bcb97" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7084-a062-584f7cab61bf" xlink:to="loc_srt_ProductOrServiceAxis_019d76fd-5fc1-7201-9450-18b08e6bcb97" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019d76fd-5fc1-7201-9450-18b08e6bcb97_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019d76fd-5fc1-7201-9450-18b08e6bcb97" xlink:to="loc_srt_ProductsAndServicesDomain_019d76fd-5fc1-7201-9450-18b08e6bcb97_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019d76fd-5fc1-7ca4-97e9-62f9ceaa23c8" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019d76fd-5fc1-7201-9450-18b08e6bcb97" xlink:to="loc_srt_ProductsAndServicesDomain_019d76fd-5fc1-7ca4-97e9-62f9ceaa23c8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoveryMember_019d76fd-5fc1-78ff-b4a2-873b91561249" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoveryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019d76fd-5fc1-7ca4-97e9-62f9ceaa23c8" xlink:to="loc_sdgr_DrugDiscoveryMember_019d76fd-5fc1-78ff-b4a2-873b91561249" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_019d76fd-5fc1-71b9-9be8-af0a3608d55a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7084-a062-584f7cab61bf" xlink:to="loc_us-gaap_TypeOfArrangementAxis_019d76fd-5fc1-71b9-9be8-af0a3608d55a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d76fd-5fc1-71b9-9be8-af0a3608d55a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019d76fd-5fc1-71b9-9be8-af0a3608d55a" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d76fd-5fc1-71b9-9be8-af0a3608d55a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d76fd-5fc1-7129-ba6e-1885cbff6fa9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019d76fd-5fc1-71b9-9be8-af0a3608d55a" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d76fd-5fc1-7129-ba6e-1885cbff6fa9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_AgreementWithGatesVenturesLimitedLiabilityCompanyMember_019d76fd-5fc1-7a2b-add0-71a0e03e2f65" xlink:href="sdgr-20260331.xsd#sdgr_AgreementWithGatesVenturesLimitedLiabilityCompanyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d76fd-5fc1-7129-ba6e-1885cbff6fa9" xlink:to="loc_sdgr_AgreementWithGatesVenturesLimitedLiabilityCompanyMember_019d76fd-5fc1-7a2b-add0-71a0e03e2f65" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_July2024AgreementWithBillMelindaGatesFoundationMember_019d76fd-5fc1-75b1-b9fd-a90fbf64dce7" xlink:href="sdgr-20260331.xsd#sdgr_July2024AgreementWithBillMelindaGatesFoundationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d76fd-5fc1-7129-ba6e-1885cbff6fa9" xlink:to="loc_sdgr_July2024AgreementWithBillMelindaGatesFoundationMember_019d76fd-5fc1-75b1-b9fd-a90fbf64dce7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_019dd24a-9fec-72b2-a402-0fe8d251c3d5" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7084-a062-584f7cab61bf" xlink:to="loc_srt_CounterpartyNameAxis_019dd24a-9fec-72b2-a402-0fe8d251c3d5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019dd24a-9fec-72b2-a402-0fe8d251c3d5_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_019dd24a-9fec-72b2-a402-0fe8d251c3d5" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019dd24a-9fec-72b2-a402-0fe8d251c3d5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019dd24a-9fec-7458-aa75-45eb9569bceb" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_019dd24a-9fec-72b2-a402-0fe8d251c3d5" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019dd24a-9fec-7458-aa75-45eb9569bceb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_BillAndMelindaGatesFoundationTrustMember_019dd24a-9fec-7902-a2ea-ccac3d81bed1" xlink:href="sdgr-20260331.xsd#sdgr_BillAndMelindaGatesFoundationTrustMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019dd24a-9fec-7458-aa75-45eb9569bceb" xlink:to="loc_sdgr_BillAndMelindaGatesFoundationTrustMember_019dd24a-9fec-7902-a2ea-ccac3d81bed1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019dd24a-9fec-7643-aee5-b092a588efd0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7084-a062-584f7cab61bf" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019dd24a-9fec-7643-aee5-b092a588efd0" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019dd24a-9fec-7643-aee5-b092a588efd0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019dd24a-9fec-7643-aee5-b092a588efd0" xlink:to="loc_us-gaap_RelatedPartyDomain_019dd24a-9fec-7643-aee5-b092a588efd0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019dd24a-9fec-7cfe-87cf-b76288ea321e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019dd24a-9fec-7643-aee5-b092a588efd0" xlink:to="loc_us-gaap_RelatedPartyDomain_019dd24a-9fec-7cfe-87cf-b76288ea321e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyMember_019dd24a-9fec-75fe-b802-fcb0264778d5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_019dd24a-9fec-7cfe-87cf-b76288ea321e" xlink:to="loc_us-gaap_RelatedPartyMember_019dd24a-9fec-75fe-b802-fcb0264778d5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_MilestonePaymentYetToBeAchieved_019d76fd-5fc1-7672-b958-609b3e53f976" xlink:href="sdgr-20260331.xsd#sdgr_MilestonePaymentYetToBeAchieved"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fd-5fc1-7e23-8ab0-d0128e4823c0" xlink:to="loc_sdgr_MilestonePaymentYetToBeAchieved_019d76fd-5fc1-7672-b958-609b3e53f976" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RevenueRecognizedForMilestonePayment_019d76fd-5fc1-7435-b5ad-c7d8f3eb7673" xlink:href="sdgr-20260331.xsd#sdgr_RevenueRecognizedForMilestonePayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fd-5fc1-7e23-8ab0-d0128e4823c0" xlink:to="loc_sdgr_RevenueRecognizedForMilestonePayment_019d76fd-5fc1-7435-b5ad-c7d8f3eb7673" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareContributionRevenueRecognitionAmount_019d76fd-5fc1-744e-9b93-a9ff6b24fcdb" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareContributionRevenueRecognitionAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fd-5fc1-7e23-8ab0-d0128e4823c0" xlink:to="loc_sdgr_SoftwareContributionRevenueRecognitionAmount_019d76fd-5fc1-744e-9b93-a9ff6b24fcdb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareContributionRevenueRecognized_019d76fd-5fc1-75fc-9b78-77020a105dec" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareContributionRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fd-5fc1-7e23-8ab0-d0128e4823c0" xlink:to="loc_sdgr_SoftwareContributionRevenueRecognized_019d76fd-5fc1-75fc-9b78-77020a105dec" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredIncome_019d76fd-5fc1-7c5e-a129-5dc3d1863351" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DeferredIncome"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fd-5fc1-7e23-8ab0-d0128e4823c0" xlink:to="loc_us-gaap_DeferredIncome_019d76fd-5fc1-7c5e-a129-5dc3d1863351" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_019d76fd-5fc1-73eb-b8ea-c27f1fcfdfc4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fd-5fc1-7e23-8ab0-d0128e4823c0" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_019d76fd-5fc1-73eb-b8ea-c27f1fcfdfc4" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueNotFromContractWithCustomer_019dd24a-9fec-7df8-8710-c08c23d1acd5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueNotFromContractWithCustomer"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fd-5fc1-7e23-8ab0-d0128e4823c0" xlink:to="loc_us-gaap_RevenueNotFromContractWithCustomer_019dd24a-9fec-7df8-8710-c08c23d1acd5" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredRevenue_019d76fd-5fc1-72de-b386-e67001d0bc97" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DeferredRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d76fd-5fc1-7e23-8ab0-d0128e4823c0" xlink:to="loc_us-gaap_DeferredRevenue_019d76fd-5fc1-72de-b386-e67001d0bc97" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionScheduleofContributionRevenueDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionScheduleofContributionRevenueDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionScheduleofContributionRevenueDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-7c87-80f0-a3d68302ae82" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7ee5-bc46-c64371e45255" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-7c87-80f0-a3d68302ae82" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7ee5-bc46-c64371e45255" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-759c-8e33-9128a00db9e8" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7ee5-bc46-c64371e45255" xlink:to="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-759c-8e33-9128a00db9e8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-759c-8e33-9128a00db9e8_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-759c-8e33-9128a00db9e8" xlink:to="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-759c-8e33-9128a00db9e8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-72b4-bec2-0177a1b36227" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-759c-8e33-9128a00db9e8" xlink:to="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-72b4-bec2-0177a1b36227" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareContributionMember_019d76f8-3964-7530-a073-bbde2e9fb1f6" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-72b4-bec2-0177a1b36227" xlink:to="loc_sdgr_SoftwareContributionMember_019d76f8-3964-7530-a073-bbde2e9fb1f6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoveryContributionMember_019dbc26-2640-76eb-833b-90087330ee8b" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoveryContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-72b4-bec2-0177a1b36227" xlink:to="loc_sdgr_DrugDiscoveryContributionMember_019dbc26-2640-76eb-833b-90087330ee8b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContributionMember_019dbf73-3b75-7a1e-b16b-a1964cdc4d6d" xlink:href="sdgr-20260331.xsd#sdgr_ContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-72b4-bec2-0177a1b36227" xlink:to="loc_sdgr_ContributionMember_019dbf73-3b75-7a1e-b16b-a1964cdc4d6d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_019cd38a-fdd8-7e95-b886-dcbdd5b541cf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-7c87-80f0-a3d68302ae82" xlink:to="loc_us-gaap_Revenues_019cd38a-fdd8-7e95-b886-dcbdd5b541cf" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionCollaborationandLicenseAgreementDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionCollaborationandLicenseAgreementDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionCollaborationandLicenseAgreementDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_019d2021-dcfc-759d-b041-002ee89f00b8" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:to="loc_srt_CounterpartyNameAxis_019d2021-dcfc-759d-b041-002ee89f00b8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-759d-b041-002ee89f00b8_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_019d2021-dcfc-759d-b041-002ee89f00b8" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-759d-b041-002ee89f00b8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-72b1-81ac-544afeafab11" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_019d2021-dcfc-759d-b041-002ee89f00b8" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-72b1-81ac-544afeafab11" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_BristolMyersSquibbMember_019d2021-dcfc-702f-8c5b-cbca0d0947b3" xlink:href="sdgr-20260331.xsd#sdgr_BristolMyersSquibbMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-72b1-81ac-544afeafab11" xlink:to="loc_sdgr_BristolMyersSquibbMember_019d2021-dcfc-702f-8c5b-cbca0d0947b3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_NovartisPharmaAGMember_019d2022-32b1-7bb5-95bd-d1380e846525" xlink:href="sdgr-20260331.xsd#sdgr_NovartisPharmaAGMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-72b1-81ac-544afeafab11" xlink:to="loc_sdgr_NovartisPharmaAGMember_019d2022-32b1-7bb5-95bd-d1380e846525" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019d2021-dcfc-7719-9bb5-1e74dde917ec" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:to="loc_srt_ProductOrServiceAxis_019d2021-dcfc-7719-9bb5-1e74dde917ec" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-7719-9bb5-1e74dde917ec_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019d2021-dcfc-7719-9bb5-1e74dde917ec" xlink:to="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-7719-9bb5-1e74dde917ec_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-790b-9445-58640fa65997" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019d2021-dcfc-7719-9bb5-1e74dde917ec" xlink:to="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-790b-9445-58640fa65997" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_OncologyNeurologyAndImmunologyProductMember_019d2021-dcfc-7442-b28c-38548bf85736" xlink:href="sdgr-20260331.xsd#sdgr_OncologyNeurologyAndImmunologyProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-790b-9445-58640fa65997" xlink:to="loc_sdgr_OncologyNeurologyAndImmunologyProductMember_019d2021-dcfc-7442-b28c-38548bf85736" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoveryServicesMember_019d2022-32b1-731e-bea2-75f99dceb586" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoveryServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-790b-9445-58640fa65997" xlink:to="loc_sdgr_DrugDiscoveryServicesMember_019d2022-32b1-731e-bea2-75f99dceb586" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_019d2022-32b1-70e8-a58f-e9b16e7f8f17" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_019d2022-32b1-70e8-a58f-e9b16e7f8f17" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_019d2022-32b1-7b30-9fd6-49d61798eb4f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:to="loc_us-gaap_TypeOfArrangementAxis_019d2022-32b1-7b30-9fd6-49d61798eb4f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7b30-9fd6-49d61798eb4f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019d2022-32b1-7b30-9fd6-49d61798eb4f" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7b30-9fd6-49d61798eb4f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7aab-a578-a5ee088e57ed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019d2022-32b1-7b30-9fd6-49d61798eb4f" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7aab-a578-a5ee088e57ed" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareAgreementMember_019d2022-32b1-7c8d-a1c7-0da50aac83a2" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7aab-a578-a5ee088e57ed" xlink:to="loc_sdgr_SoftwareAgreementMember_019d2022-32b1-7c8d-a1c7-0da50aac83a2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ResearchCollaborationAndLicenseAgreementMember_019d2022-32b1-7693-b245-2cf00c761e39" xlink:href="sdgr-20260331.xsd#sdgr_ResearchCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7aab-a578-a5ee088e57ed" xlink:to="loc_sdgr_ResearchCollaborationAndLicenseAgreementMember_019d2022-32b1-7693-b245-2cf00c761e39" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_CollaborationAndLicenseAgreementMember_019d2022-5da2-73f2-b062-7a6640529bbc" xlink:href="sdgr-20260331.xsd#sdgr_CollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7aab-a578-a5ee088e57ed" xlink:to="loc_sdgr_CollaborationAndLicenseAgreementMember_019d2022-5da2-73f2-b062-7a6640529bbc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContractWithCustomerNumberOfSpecifiedBiologicalTargets_019d2021-dcfc-7bc7-8906-5f59b7835ea0" xlink:href="sdgr-20260331.xsd#sdgr_ContractWithCustomerNumberOfSpecifiedBiologicalTargets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_ContractWithCustomerNumberOfSpecifiedBiologicalTargets_019d2021-dcfc-7bc7-8906-5f59b7835ea0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContractWithCustomerNumberOfNeurologyTargetRemaining_019d2021-dcfc-74e6-8e43-413318db9e8b" xlink:href="sdgr-20260331.xsd#sdgr_ContractWithCustomerNumberOfNeurologyTargetRemaining"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_ContractWithCustomerNumberOfNeurologyTargetRemaining_019d2021-dcfc-74e6-8e43-413318db9e8b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_019d2021-dcfc-796d-adc3-b6a7e116a976" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_ContractWithCustomerLiability_019d2021-dcfc-796d-adc3-b6a7e116a976" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationAmount_019d2021-dcfc-7b76-ae60-a9f4c30c9019" xlink:href="sdgr-20260331.xsd#sdgr_RevenueRemainingPerformanceObligationVariableConsiderationAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationAmount_019d2021-dcfc-7b76-ae60-a9f4c30c9019" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationResearchDevelopmentAndRegulatoryMilestonesAmount_019d2021-dcfc-7661-acd3-f7a53c61c1df" xlink:href="sdgr-20260331.xsd#sdgr_RevenueRemainingPerformanceObligationVariableConsiderationResearchDevelopmentAndRegulatoryMilestonesAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationResearchDevelopmentAndRegulatoryMilestonesAmount_019d2021-dcfc-7661-acd3-f7a53c61c1df" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationCommercialMilestonesAmount_019d2021-dcfc-72ae-b3ba-b65f4c880988" xlink:href="sdgr-20260331.xsd#sdgr_RevenueRemainingPerformanceObligationVariableConsiderationCommercialMilestonesAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationCommercialMilestonesAmount_019d2021-dcfc-72ae-b3ba-b65f4c880988" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_019d2021-dcfc-76a3-bd4d-fc5c7019cd6a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_019d2021-dcfc-76a3-bd4d-fc5c7019cd6a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_NumberOfPerformanceObligations_019d2022-0c02-7c49-a0aa-3f28db8cfa84" xlink:href="sdgr-20260331.xsd#sdgr_NumberOfPerformanceObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_NumberOfPerformanceObligations_019d2022-0c02-7c49-a0aa-3f28db8cfa84" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_CollaborativeAgreementNumberOfPrograms_019d2022-0c02-7c95-8a36-cc6785389a95" xlink:href="sdgr-20260331.xsd#sdgr_CollaborativeAgreementNumberOfPrograms"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_CollaborativeAgreementNumberOfPrograms_019d2022-0c02-7c95-8a36-cc6785389a95" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_019d2022-0c02-7ba5-96f9-2a9f4512c2f1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_019d2022-0c02-7ba5-96f9-2a9f4512c2f1" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019d2022-32b1-7eb2-88b6-b18e81ccde3f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019d2022-32b1-7eb2-88b6-b18e81ccde3f" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerReceivableAfterAllowanceForCreditLossCurrent_019d2022-32b1-7342-875d-0058c29cc294" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerReceivableAfterAllowanceForCreditLossCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_ContractWithCustomerReceivableAfterAllowanceForCreditLossCurrent_019d2022-32b1-7342-875d-0058c29cc294" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_019d2022-32b1-78ef-a4f2-f43c365b50ce" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_019d2022-32b1-78ef-a4f2-f43c365b50ce" xlink:type="arc" order="12"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionCollaborationandLicenseAgreementDetails_1" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionCollaborationandLicenseAgreementDetails_1"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionCollaborationandLicenseAgreementDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_019d2021-dcfc-759d-b041-002ee89f00b8" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:to="loc_srt_CounterpartyNameAxis_019d2021-dcfc-759d-b041-002ee89f00b8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-759d-b041-002ee89f00b8_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_019d2021-dcfc-759d-b041-002ee89f00b8" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-759d-b041-002ee89f00b8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-72b1-81ac-544afeafab11" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_019d2021-dcfc-759d-b041-002ee89f00b8" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-72b1-81ac-544afeafab11" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_BristolMyersSquibbMember_019d2021-dcfc-702f-8c5b-cbca0d0947b3" xlink:href="sdgr-20260331.xsd#sdgr_BristolMyersSquibbMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-72b1-81ac-544afeafab11" xlink:to="loc_sdgr_BristolMyersSquibbMember_019d2021-dcfc-702f-8c5b-cbca0d0947b3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_NovartisPharmaAGMember_019d2022-32b1-7bb5-95bd-d1380e846525" xlink:href="sdgr-20260331.xsd#sdgr_NovartisPharmaAGMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d2021-dcfc-72b1-81ac-544afeafab11" xlink:to="loc_sdgr_NovartisPharmaAGMember_019d2022-32b1-7bb5-95bd-d1380e846525" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019d2021-dcfc-7719-9bb5-1e74dde917ec" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:to="loc_srt_ProductOrServiceAxis_019d2021-dcfc-7719-9bb5-1e74dde917ec" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-7719-9bb5-1e74dde917ec_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019d2021-dcfc-7719-9bb5-1e74dde917ec" xlink:to="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-7719-9bb5-1e74dde917ec_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-790b-9445-58640fa65997" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019d2021-dcfc-7719-9bb5-1e74dde917ec" xlink:to="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-790b-9445-58640fa65997" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_OncologyNeurologyAndImmunologyProductMember_019d2021-dcfc-7442-b28c-38548bf85736" xlink:href="sdgr-20260331.xsd#sdgr_OncologyNeurologyAndImmunologyProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-790b-9445-58640fa65997" xlink:to="loc_sdgr_OncologyNeurologyAndImmunologyProductMember_019d2021-dcfc-7442-b28c-38548bf85736" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoveryServicesMember_019d2022-32b1-731e-bea2-75f99dceb586" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoveryServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019d2021-dcfc-790b-9445-58640fa65997" xlink:to="loc_sdgr_DrugDiscoveryServicesMember_019d2022-32b1-731e-bea2-75f99dceb586" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_019d2022-32b1-7b30-9fd6-49d61798eb4f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-76a2-be94-c66d2d790175" xlink:to="loc_us-gaap_TypeOfArrangementAxis_019d2022-32b1-7b30-9fd6-49d61798eb4f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7b30-9fd6-49d61798eb4f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019d2022-32b1-7b30-9fd6-49d61798eb4f" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7b30-9fd6-49d61798eb4f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7aab-a578-a5ee088e57ed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019d2022-32b1-7b30-9fd6-49d61798eb4f" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7aab-a578-a5ee088e57ed" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareAgreementMember_019d2022-32b1-7c8d-a1c7-0da50aac83a2" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7aab-a578-a5ee088e57ed" xlink:to="loc_sdgr_SoftwareAgreementMember_019d2022-32b1-7c8d-a1c7-0da50aac83a2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ResearchCollaborationAndLicenseAgreementMember_019d2022-32b1-7693-b245-2cf00c761e39" xlink:href="sdgr-20260331.xsd#sdgr_ResearchCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7aab-a578-a5ee088e57ed" xlink:to="loc_sdgr_ResearchCollaborationAndLicenseAgreementMember_019d2022-32b1-7693-b245-2cf00c761e39" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_CollaborationAndLicenseAgreementMember_019d2022-5da2-73f2-b062-7a6640529bbc" xlink:href="sdgr-20260331.xsd#sdgr_CollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d2022-32b1-7aab-a578-a5ee088e57ed" xlink:to="loc_sdgr_CollaborationAndLicenseAgreementMember_019d2022-5da2-73f2-b062-7a6640529bbc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContractWithCustomerNumberOfSpecifiedBiologicalTargets_019d2021-dcfc-7bc7-8906-5f59b7835ea0" xlink:href="sdgr-20260331.xsd#sdgr_ContractWithCustomerNumberOfSpecifiedBiologicalTargets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_ContractWithCustomerNumberOfSpecifiedBiologicalTargets_019d2021-dcfc-7bc7-8906-5f59b7835ea0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContractWithCustomerNumberOfNeurologyTargetRemaining_019d2021-dcfc-74e6-8e43-413318db9e8b" xlink:href="sdgr-20260331.xsd#sdgr_ContractWithCustomerNumberOfNeurologyTargetRemaining"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_ContractWithCustomerNumberOfNeurologyTargetRemaining_019d2021-dcfc-74e6-8e43-413318db9e8b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_019d2021-dcfc-796d-adc3-b6a7e116a976" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_ContractWithCustomerLiability_019d2021-dcfc-796d-adc3-b6a7e116a976" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationAmount_019d2021-dcfc-7b76-ae60-a9f4c30c9019" xlink:href="sdgr-20260331.xsd#sdgr_RevenueRemainingPerformanceObligationVariableConsiderationAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationAmount_019d2021-dcfc-7b76-ae60-a9f4c30c9019" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationResearchDevelopmentAndRegulatoryMilestonesAmount_019d2021-dcfc-7661-acd3-f7a53c61c1df" xlink:href="sdgr-20260331.xsd#sdgr_RevenueRemainingPerformanceObligationVariableConsiderationResearchDevelopmentAndRegulatoryMilestonesAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationResearchDevelopmentAndRegulatoryMilestonesAmount_019d2021-dcfc-7661-acd3-f7a53c61c1df" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationCommercialMilestonesAmount_019d2021-dcfc-72ae-b3ba-b65f4c880988" xlink:href="sdgr-20260331.xsd#sdgr_RevenueRemainingPerformanceObligationVariableConsiderationCommercialMilestonesAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_RevenueRemainingPerformanceObligationVariableConsiderationCommercialMilestonesAmount_019d2021-dcfc-72ae-b3ba-b65f4c880988" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_019d2021-dcfc-76a3-bd4d-fc5c7019cd6a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_019d2021-dcfc-76a3-bd4d-fc5c7019cd6a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_NumberOfPerformanceObligations_019d2022-0c02-7c49-a0aa-3f28db8cfa84" xlink:href="sdgr-20260331.xsd#sdgr_NumberOfPerformanceObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_NumberOfPerformanceObligations_019d2022-0c02-7c49-a0aa-3f28db8cfa84" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_CollaborativeAgreementNumberOfPrograms_019d2022-0c02-7c95-8a36-cc6785389a95" xlink:href="sdgr-20260331.xsd#sdgr_CollaborativeAgreementNumberOfPrograms"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_sdgr_CollaborativeAgreementNumberOfPrograms_019d2022-0c02-7c95-8a36-cc6785389a95" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_019d2022-0c02-7ba5-96f9-2a9f4512c2f1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_019d2022-0c02-7ba5-96f9-2a9f4512c2f1" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019d2022-32b1-7eb2-88b6-b18e81ccde3f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019d2022-32b1-7eb2-88b6-b18e81ccde3f" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerReceivableAfterAllowanceForCreditLossCurrent_019d2022-32b1-7342-875d-0058c29cc294" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerReceivableAfterAllowanceForCreditLossCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_ContractWithCustomerReceivableAfterAllowanceForCreditLossCurrent_019d2022-32b1-7342-875d-0058c29cc294" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_019d2022-32b1-78ef-a4f2-f43c365b50ce" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019d2021-dcfc-79e8-9323-332cbd70cd2c" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_019d2022-32b1-78ef-a4f2-f43c365b50ce" xlink:type="arc" order="12"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionContractBalancesDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionContractBalancesDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionContractBalancesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7fe6-abe0-06af98c09576" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7fe6-abe0-06af98c09576" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019cd38a-fdd8-7316-8310-372519f9b3fe" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7fe6-abe0-06af98c09576" xlink:to="loc_srt_RangeAxis_019cd38a-fdd8-7316-8310-372519f9b3fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019cd38a-fdd8-7316-8310-372519f9b3fe_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019cd38a-fdd8-7316-8310-372519f9b3fe" xlink:to="loc_srt_RangeMember_019cd38a-fdd8-7316-8310-372519f9b3fe_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019cd38a-fdd8-77c6-a437-e44c4001f1cf" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019cd38a-fdd8-7316-8310-372519f9b3fe" xlink:to="loc_srt_RangeMember_019cd38a-fdd8-77c6-a437-e44c4001f1cf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_019cd38a-fdd8-7713-8338-ae1e4e7d733e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019cd38a-fdd8-77c6-a437-e44c4001f1cf" xlink:to="loc_srt_MinimumMember_019cd38a-fdd8-7713-8338-ae1e4e7d733e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_019cd38a-fdd8-7ac8-89ad-95084da85abf" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019cd38a-fdd8-77c6-a437-e44c4001f1cf" xlink:to="loc_srt_MaximumMember_019cd38a-fdd8-7ac8-89ad-95084da85abf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019dadf7-5651-79dc-adba-32125038230a" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7fe6-abe0-06af98c09576" xlink:to="loc_srt_ProductOrServiceAxis_019dadf7-5651-79dc-adba-32125038230a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019dadf7-5651-79dc-adba-32125038230a_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019dadf7-5651-79dc-adba-32125038230a" xlink:to="loc_srt_ProductsAndServicesDomain_019dadf7-5651-79dc-adba-32125038230a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019dadf7-5651-78e3-8383-19332b418c1e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019dadf7-5651-79dc-adba-32125038230a" xlink:to="loc_srt_ProductsAndServicesDomain_019dadf7-5651-78e3-8383-19332b418c1e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareProductsAndServicesMember_019dadf7-5651-7a69-b8e6-cab69464d57a" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareProductsAndServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019dadf7-5651-78e3-8383-19332b418c1e" xlink:to="loc_sdgr_SoftwareProductsAndServicesMember_019dadf7-5651-7a69-b8e6-cab69464d57a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoveryMember_019dadf7-5651-7fa6-8ac6-3ea5425e2178" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoveryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019dadf7-5651-78e3-8383-19332b418c1e" xlink:to="loc_sdgr_DrugDiscoveryMember_019dadf7-5651-7fa6-8ac6-3ea5425e2178" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContributionMember_019dadf7-5651-73c8-89f4-d6206cef879f" xlink:href="sdgr-20260331.xsd#sdgr_ContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019dadf7-5651-78e3-8383-19332b418c1e" xlink:to="loc_sdgr_ContributionMember_019dadf7-5651-73c8-89f4-d6206cef879f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_019dd733-97a2-702b-bc74-f1f8849ea722" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7fe6-abe0-06af98c09576" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_019dd733-97a2-702b-bc74-f1f8849ea722" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_019cd38a-fdd8-79e5-8d99-4b5ff1f0480e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_019cd38a-fdd8-79e5-8d99-4b5ff1f0480e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_019dd742-b630-74ac-bcf3-e349badcff80" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_019dd742-b630-74ac-bcf3-e349badcff80" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_019dd733-3287-7a7b-882c-43450d84e476" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_019dd733-3287-7a7b-882c-43450d84e476" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContractWithCustomersPaymentTerms_019cd38a-fdd9-7363-b52f-c554617a7d45" xlink:href="sdgr-20260331.xsd#sdgr_ContractWithCustomersPaymentTerms"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:to="loc_sdgr_ContractWithCustomersPaymentTerms_019cd38a-fdd9-7363-b52f-c554617a7d45" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionContractBalancesDetails_1" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionContractBalancesDetails_1"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionContractBalancesDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7fe6-abe0-06af98c09576" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7fe6-abe0-06af98c09576" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019cd38a-fdd8-7316-8310-372519f9b3fe" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7fe6-abe0-06af98c09576" xlink:to="loc_srt_RangeAxis_019cd38a-fdd8-7316-8310-372519f9b3fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019cd38a-fdd8-7316-8310-372519f9b3fe_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019cd38a-fdd8-7316-8310-372519f9b3fe" xlink:to="loc_srt_RangeMember_019cd38a-fdd8-7316-8310-372519f9b3fe_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019cd38a-fdd8-77c6-a437-e44c4001f1cf" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019cd38a-fdd8-7316-8310-372519f9b3fe" xlink:to="loc_srt_RangeMember_019cd38a-fdd8-77c6-a437-e44c4001f1cf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_019cd38a-fdd8-7713-8338-ae1e4e7d733e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019cd38a-fdd8-77c6-a437-e44c4001f1cf" xlink:to="loc_srt_MinimumMember_019cd38a-fdd8-7713-8338-ae1e4e7d733e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_019cd38a-fdd8-7ac8-89ad-95084da85abf" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019cd38a-fdd8-77c6-a437-e44c4001f1cf" xlink:to="loc_srt_MaximumMember_019cd38a-fdd8-7ac8-89ad-95084da85abf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019dadf7-5651-79dc-adba-32125038230a" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionTable_019cd38a-fdd8-7fe6-abe0-06af98c09576" xlink:to="loc_srt_ProductOrServiceAxis_019dadf7-5651-79dc-adba-32125038230a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019dadf7-5651-79dc-adba-32125038230a_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019dadf7-5651-79dc-adba-32125038230a" xlink:to="loc_srt_ProductsAndServicesDomain_019dadf7-5651-79dc-adba-32125038230a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019dadf7-5651-78e3-8383-19332b418c1e" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019dadf7-5651-79dc-adba-32125038230a" xlink:to="loc_srt_ProductsAndServicesDomain_019dadf7-5651-78e3-8383-19332b418c1e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareProductsAndServicesMember_019dadf7-5651-7a69-b8e6-cab69464d57a" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareProductsAndServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019dadf7-5651-78e3-8383-19332b418c1e" xlink:to="loc_sdgr_SoftwareProductsAndServicesMember_019dadf7-5651-7a69-b8e6-cab69464d57a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoveryMember_019dadf7-5651-7fa6-8ac6-3ea5425e2178" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoveryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019dadf7-5651-78e3-8383-19332b418c1e" xlink:to="loc_sdgr_DrugDiscoveryMember_019dadf7-5651-7fa6-8ac6-3ea5425e2178" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContributionMember_019dadf7-5651-73c8-89f4-d6206cef879f" xlink:href="sdgr-20260331.xsd#sdgr_ContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019dadf7-5651-78e3-8383-19332b418c1e" xlink:to="loc_sdgr_ContributionMember_019dadf7-5651-73c8-89f4-d6206cef879f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_019cd38a-fdd8-79e5-8d99-4b5ff1f0480e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_019cd38a-fdd8-79e5-8d99-4b5ff1f0480e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_019dd742-b630-74ac-bcf3-e349badcff80" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationPercentage_019dd742-b630-74ac-bcf3-e349badcff80" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_019dd733-3287-7a7b-882c-43450d84e476" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_019dd733-3287-7a7b-882c-43450d84e476" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContractWithCustomersPaymentTerms_019cd38a-fdd9-7363-b52f-c554617a7d45" xlink:href="sdgr-20260331.xsd#sdgr_ContractWithCustomersPaymentTerms"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionLineItems_019cd38a-fdd8-7d5c-b9c5-78d91a432c26" xlink:to="loc_sdgr_ContractWithCustomersPaymentTerms_019cd38a-fdd9-7363-b52f-c554617a7d45" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionScheduleofContractBalancesDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionScheduleofContractBalancesDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionScheduleofContractBalancesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-74aa-93f3-1e7a6e7e0b1d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7efe-9e71-847c6d1ce77e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-74aa-93f3-1e7a6e7e0b1d" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7efe-9e71-847c6d1ce77e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7642-acf4-d83baca8d4a8" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019cd38a-fdd8-7efe-9e71-847c6d1ce77e" xlink:to="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7642-acf4-d83baca8d4a8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7642-acf4-d83baca8d4a8_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7642-acf4-d83baca8d4a8" xlink:to="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7642-acf4-d83baca8d4a8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7ebd-ac46-65f71916fdd0" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019cd38a-fdd8-7642-acf4-d83baca8d4a8" xlink:to="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7ebd-ac46-65f71916fdd0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareProductsAndServicesMember_019cd38a-fdd8-7258-90da-1cd9bc62f6e5" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareProductsAndServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7ebd-ac46-65f71916fdd0" xlink:to="loc_sdgr_SoftwareProductsAndServicesMember_019cd38a-fdd8-7258-90da-1cd9bc62f6e5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoveryMember_019cd38a-fdd8-7cce-a711-6063678b5778" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoveryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7ebd-ac46-65f71916fdd0" xlink:to="loc_sdgr_DrugDiscoveryMember_019cd38a-fdd8-7cce-a711-6063678b5778" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContributionMember_019d76f6-5ab9-7e77-8828-8654439ba5ae" xlink:href="sdgr-20260331.xsd#sdgr_ContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019cd38a-fdd8-7ebd-ac46-65f71916fdd0" xlink:to="loc_sdgr_ContributionMember_019d76f6-5ab9-7e77-8828-8654439ba5ae" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerAssetNet_019cd38a-fdd8-77f8-bfad-b942d69961aa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerAssetNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-74aa-93f3-1e7a6e7e0b1d" xlink:to="loc_us-gaap_ContractWithCustomerAssetNet_019cd38a-fdd8-77f8-bfad-b942d69961aa" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredRevenueAndCreditsCurrentAbstract_019cd38a-fdd8-7b14-8afe-9ed0b4b075d5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DeferredRevenueAndCreditsCurrentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-74aa-93f3-1e7a6e7e0b1d" xlink:to="loc_us-gaap_DeferredRevenueAndCreditsCurrentAbstract_019cd38a-fdd8-7b14-8afe-9ed0b4b075d5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_019cd38a-fdd8-70f2-aeed-869b29a198aa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DeferredRevenueAndCreditsCurrentAbstract_019cd38a-fdd8-7b14-8afe-9ed0b4b075d5" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_019cd38a-fdd8-70f2-aeed-869b29a198aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredRevenueAndCreditsNoncurrentAbstract_019cd38a-fdd8-7767-b9bc-824a6aaadc07" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DeferredRevenueAndCreditsNoncurrentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019cd38a-fdd8-74aa-93f3-1e7a6e7e0b1d" xlink:to="loc_us-gaap_DeferredRevenueAndCreditsNoncurrentAbstract_019cd38a-fdd8-7767-b9bc-824a6aaadc07" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_019cd38a-fdd8-7a66-9e81-a1dd11816f51" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DeferredRevenueAndCreditsNoncurrentAbstract_019cd38a-fdd8-7767-b9bc-824a6aaadc07" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_019cd38a-fdd8-7a66-9e81-a1dd11816f51" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RevenueRecognitionScheduleofRemainingPerformanceObligationsDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RevenueRecognitionScheduleofRemainingPerformanceObligationsDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RevenueRecognitionScheduleofRemainingPerformanceObligationsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_019dae40-7f3f-7327-9d72-fdd4e6c5bd8e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_019dae40-7f3f-775f-983f-6158a2988bf6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019dae40-7f3f-7327-9d72-fdd4e6c5bd8e" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_019dae40-7f3f-775f-983f-6158a2988bf6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019dae40-7f3f-7c40-9df3-57e8d7cc8b1f" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_019dae40-7f3f-775f-983f-6158a2988bf6" xlink:to="loc_srt_ProductOrServiceAxis_019dae40-7f3f-7c40-9df3-57e8d7cc8b1f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019dae40-7f3f-7c40-9df3-57e8d7cc8b1f_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019dae40-7f3f-7c40-9df3-57e8d7cc8b1f" xlink:to="loc_srt_ProductsAndServicesDomain_019dae40-7f3f-7c40-9df3-57e8d7cc8b1f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019dae40-7f3f-7fe3-ad11-a00d7795b929" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019dae40-7f3f-7c40-9df3-57e8d7cc8b1f" xlink:to="loc_srt_ProductsAndServicesDomain_019dae40-7f3f-7fe3-ad11-a00d7795b929" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareProductsAndServicesMember_019dae40-7f3f-71b9-9c83-1ef3c89ab585" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareProductsAndServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019dae40-7f3f-7fe3-ad11-a00d7795b929" xlink:to="loc_sdgr_SoftwareProductsAndServicesMember_019dae40-7f3f-71b9-9c83-1ef3c89ab585" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoveryMember_019dae40-7f3f-7681-9462-66dd07c88dd2" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoveryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019dae40-7f3f-7fe3-ad11-a00d7795b929" xlink:to="loc_sdgr_DrugDiscoveryMember_019dae40-7f3f-7681-9462-66dd07c88dd2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContributionMember_019dae40-7f3f-7119-abce-0983d8a1df7f" xlink:href="sdgr-20260331.xsd#sdgr_ContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019dae40-7f3f-7fe3-ad11-a00d7795b929" xlink:to="loc_sdgr_ContributionMember_019dae40-7f3f-7119-abce-0983d8a1df7f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RevenueRemainingPerformanceObligationDeferredRevenue_019dae40-7f3f-7297-985d-611550333ae8" xlink:href="sdgr-20260331.xsd#sdgr_RevenueRemainingPerformanceObligationDeferredRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019dae40-7f3f-7327-9d72-fdd4e6c5bd8e" xlink:to="loc_sdgr_RevenueRemainingPerformanceObligationDeferredRevenue_019dae40-7f3f-7297-985d-611550333ae8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RevenueRemainingPerformanceObligationBacklog_019dbf66-8706-7cf3-8c4b-91d2c6427e9d" xlink:href="sdgr-20260331.xsd#sdgr_RevenueRemainingPerformanceObligationBacklog"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019dae40-7f3f-7327-9d72-fdd4e6c5bd8e" xlink:to="loc_sdgr_RevenueRemainingPerformanceObligationBacklog_019dbf66-8706-7cf3-8c4b-91d2c6427e9d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_019dae40-7f3f-7e4a-9cae-736c4addf34a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_019dae40-7f3f-7327-9d72-fdd4e6c5bd8e" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_019dae40-7f3f-7e4a-9cae-736c4addf34a" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#FairValueMeasurementsDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/FairValueMeasurementsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems_019d2045-2562-7517-95f7-9161323f730e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByBalanceSheetGroupingTable_019cd38a-fdd9-7d52-a3c9-8264c674eef4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueByBalanceSheetGroupingTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems_019d2045-2562-7517-95f7-9161323f730e" xlink:to="loc_us-gaap_FairValueByBalanceSheetGroupingTable_019cd38a-fdd9-7d52-a3c9-8264c674eef4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019d2045-2562-7875-b1fe-88079e719fb3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueByBalanceSheetGroupingTable_019cd38a-fdd9-7d52-a3c9-8264c674eef4" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019d2045-2562-7875-b1fe-88079e719fb3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019d2045-2562-7875-b1fe-88079e719fb3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019d2045-2562-7875-b1fe-88079e719fb3" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019d2045-2562-7875-b1fe-88079e719fb3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019d2045-2562-7234-95f3-b904987bef48" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019d2045-2562-7875-b1fe-88079e719fb3" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019d2045-2562-7234-95f3-b904987bef48" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_019d2045-2562-75e7-b41c-9078daef2d81" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019d2045-2562-7234-95f3-b904987bef48" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_019d2045-2562-75e7-b41c-9078daef2d81" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_019d2045-2562-7da6-9e67-47c7d0c03c63" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019d2045-2562-7234-95f3-b904987bef48" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_019d2045-2562-7da6-9e67-47c7d0c03c63" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_019d2045-2562-7dd6-8735-139bc43521e8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019d2045-2562-7234-95f3-b904987bef48" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_019d2045-2562-7dd6-8735-139bc43521e8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_019d2045-7f10-734b-9e01-2740db974fde" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems_019d2045-2562-7517-95f7-9161323f730e" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_019d2045-7f10-734b-9e01-2740db974fde" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_019d2045-2562-77bd-bea7-cdb23555deb1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_019d2045-7f10-734b-9e01-2740db974fde" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_019d2045-2562-77bd-bea7-cdb23555deb1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019d2045-2562-7870-ad74-69966df25d6f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_019d2045-7f10-734b-9e01-2740db974fde" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_019d2045-2562-7870-ad74-69966df25d6f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentsFairValueDisclosure_019d2045-2562-739a-ade0-9d2ba7f14c2a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquityMethodInvestmentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_019d2045-7f10-734b-9e01-2740db974fde" xlink:to="loc_us-gaap_EquityMethodInvestmentsFairValueDisclosure_019d2045-2562-739a-ade0-9d2ba7f14c2a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_019d2045-2562-7b1c-9027-58ffb58d509c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_019d2045-7f10-734b-9e01-2740db974fde" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_019d2045-2562-7b1c-9027-58ffb58d509c" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/StockholdersEquityDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#StockholdersEquityDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/StockholdersEquityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_019cd38a-fdd9-7150-80f0-b9419eb20643" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_019cd38a-fdd9-7150-80f0-b9419eb20643" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd9-75fc-a9fa-2388685722f6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_019cd38a-fdd9-7150-80f0-b9419eb20643" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd9-75fc-a9fa-2388685722f6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd9-75fc-a9fa-2388685722f6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd9-75fc-a9fa-2388685722f6" xlink:to="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd9-75fc-a9fa-2388685722f6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd9-7224-afd7-b376199ceee3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019cd38a-fdd9-75fc-a9fa-2388685722f6" xlink:to="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd9-7224-afd7-b376199ceee3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_VotingCommonStockMember_019cd38a-fdd9-726c-9443-d38e4a0cc347" xlink:href="sdgr-20260331.xsd#sdgr_VotingCommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd9-7224-afd7-b376199ceee3" xlink:to="loc_sdgr_VotingCommonStockMember_019cd38a-fdd9-726c-9443-d38e4a0cc347" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_LimitedCommonStockMember_019cd38a-fdd9-7b9f-b713-30d6c498c9fb" xlink:href="sdgr-20260331.xsd#sdgr_LimitedCommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019cd38a-fdd9-7224-afd7-b376199ceee3" xlink:to="loc_sdgr_LimitedCommonStockMember_019cd38a-fdd9-7b9f-b713-30d6c498c9fb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_019cd38a-fdd9-768c-a485-012f7803a74c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_019cd38a-fdd9-7150-80f0-b9419eb20643" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_019cd38a-fdd9-768c-a485-012f7803a74c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019cd38a-fdd9-768c-a485-012f7803a74c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_019cd38a-fdd9-768c-a485-012f7803a74c" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019cd38a-fdd9-768c-a485-012f7803a74c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019cd38a-fdd9-7f5a-9ab3-9ba32828fdd5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_019cd38a-fdd9-768c-a485-012f7803a74c" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019cd38a-fdd9-7f5a-9ab3-9ba32828fdd5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_TheATMMember_019cd38a-fdd9-76b7-8ddb-4b6cdc12f9af" xlink:href="sdgr-20260331.xsd#sdgr_TheATMMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_019cd38a-fdd9-7f5a-9ab3-9ba32828fdd5" xlink:to="loc_sdgr_TheATMMember_019cd38a-fdd9-76b7-8ddb-4b6cdc12f9af" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesAuthorized_019cd38a-fdd9-7ff5-9b4a-8a99e58194ad" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:to="loc_us-gaap_CommonStockSharesAuthorized_019cd38a-fdd9-7ff5-9b4a-8a99e58194ad" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_019cd38a-fdd9-7360-90d7-96a8ff45bd1d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_019cd38a-fdd9-7360-90d7-96a8ff45bd1d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_NumberOfVotesForCommonShare_019cd38a-fdd9-77ab-b5bf-5654ec81a833" xlink:href="sdgr-20260331.xsd#sdgr_NumberOfVotesForCommonShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:to="loc_sdgr_NumberOfVotesForCommonShare_019cd38a-fdd9-77ab-b5bf-5654ec81a833" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_019cd38a-fdd9-7744-9d0c-40a4fe0b5086" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_019cd38a-fdd9-7744-9d0c-40a4fe0b5086" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_019cd38a-fdd9-79ff-a04a-3343abcc5dcf" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_019cd38a-fdd9-79ff-a04a-3343abcc5dcf" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SaleOfStockRemainingValueOfSharesAvailableForIssuance_019cd38a-fdd9-7024-bb57-7a088e826fa3" xlink:href="sdgr-20260331.xsd#sdgr_SaleOfStockRemainingValueOfSharesAvailableForIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:to="loc_sdgr_SaleOfStockRemainingValueOfSharesAvailableForIssuance_019cd38a-fdd9-7024-bb57-7a088e826fa3" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_RightToExchangeEachShareOfLimitedCommonStockToCommonStock_019cd38a-fdd9-7f60-bda1-c83cd468b6d0" xlink:href="sdgr-20260331.xsd#sdgr_RightToExchangeEachShareOfLimitedCommonStockToCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:to="loc_sdgr_RightToExchangeEachShareOfLimitedCommonStockToCommonStock_019cd38a-fdd9-7f60-bda1-c83cd468b6d0" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesAuthorized_019cd38a-fdd9-7b7e-8372-a895c679b287" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PreferredStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:to="loc_us-gaap_PreferredStockSharesAuthorized_019cd38a-fdd9-7b7e-8372-a895c679b287" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019cd38a-fdd9-77af-8ddc-fcdf31acb262" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PreferredStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019cd38a-fdd9-7dd8-af13-502aa646b8c1" xlink:to="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019cd38a-fdd9-77af-8ddc-fcdf31acb262" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/StockBasedCompensationAdditionalInformationDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#StockBasedCompensationAdditionalInformationDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/StockBasedCompensationAdditionalInformationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cd38a-fdd9-7be2-beec-d05c96d68fd1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cd38a-fdd9-7be2-beec-d05c96d68fd1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019d3360-a6a0-7456-bf7b-9e604d082a66" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cd38a-fdd9-7be2-beec-d05c96d68fd1" xlink:to="loc_us-gaap_PlanNameAxis_019d3360-a6a0-7456-bf7b-9e604d082a66" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019d3360-a6a0-7456-bf7b-9e604d082a66_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019d3360-a6a0-7456-bf7b-9e604d082a66" xlink:to="loc_us-gaap_PlanNameDomain_019d3360-a6a0-7456-bf7b-9e604d082a66_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019d3360-a6a0-7f02-95fe-1b2e09058413" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019d3360-a6a0-7456-bf7b-9e604d082a66" xlink:to="loc_us-gaap_PlanNameDomain_019d3360-a6a0-7f02-95fe-1b2e09058413" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_TwentyTwentyStockPlanMember_019d336a-4d8c-7867-bbc8-a0240040b65e" xlink:href="sdgr-20260331.xsd#sdgr_TwentyTwentyStockPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019d3360-a6a0-7f02-95fe-1b2e09058413" xlink:to="loc_sdgr_TwentyTwentyStockPlanMember_019d336a-4d8c-7867-bbc8-a0240040b65e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_TwoThousandTenStockPlanMember_019d3360-a6a0-74dc-8b2f-a2d39dfbe292" xlink:href="sdgr-20260331.xsd#sdgr_TwoThousandTenStockPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019d3360-a6a0-7f02-95fe-1b2e09058413" xlink:to="loc_sdgr_TwoThousandTenStockPlanMember_019d3360-a6a0-74dc-8b2f-a2d39dfbe292" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019d3360-c208-78fc-b766-bf337d0e61d9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cd38a-fdd9-7be2-beec-d05c96d68fd1" xlink:to="loc_us-gaap_AwardTypeAxis_019d3360-c208-78fc-b766-bf337d0e61d9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d3360-c208-78fc-b766-bf337d0e61d9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019d3360-c208-78fc-b766-bf337d0e61d9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d3360-c208-78fc-b766-bf337d0e61d9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d3360-c208-7551-9bd6-03c0a92a23ee" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019d3360-c208-78fc-b766-bf337d0e61d9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d3360-c208-7551-9bd6-03c0a92a23ee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019d3360-c208-76a5-97a8-52be11e9ed0a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d3360-c208-7551-9bd6-03c0a92a23ee" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019d3360-c208-76a5-97a8-52be11e9ed0a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_PerformanceBasedRestrictedStockUnitsMember_019d3360-e7b1-7c09-b223-2a7ee6c7bc6f" xlink:href="sdgr-20260331.xsd#sdgr_PerformanceBasedRestrictedStockUnitsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d3360-c208-7551-9bd6-03c0a92a23ee" xlink:to="loc_sdgr_PerformanceBasedRestrictedStockUnitsMember_019d3360-e7b1-7c09-b223-2a7ee6c7bc6f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_EligiblePerformanceBasedRestrictedStockUnitsMember_019d3360-e7b1-7323-ab7d-fca0b9c65d3a" xlink:href="sdgr-20260331.xsd#sdgr_EligiblePerformanceBasedRestrictedStockUnitsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d3360-c208-7551-9bd6-03c0a92a23ee" xlink:to="loc_sdgr_EligiblePerformanceBasedRestrictedStockUnitsMember_019d3360-e7b1-7323-ab7d-fca0b9c65d3a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_019d3361-1543-78f2-a353-6a83948760c7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019d3360-c208-7551-9bd6-03c0a92a23ee" xlink:to="loc_us-gaap_EmployeeStockOptionMember_019d3361-1543-78f2-a353-6a83948760c7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VestingAxis_019d3360-c208-792e-8a01-3e6cfc34783f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VestingAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cd38a-fdd9-7be2-beec-d05c96d68fd1" xlink:to="loc_us-gaap_VestingAxis_019d3360-c208-792e-8a01-3e6cfc34783f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VestingDomain_019d3360-c208-792e-8a01-3e6cfc34783f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VestingDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_VestingAxis_019d3360-c208-792e-8a01-3e6cfc34783f" xlink:to="loc_us-gaap_VestingDomain_019d3360-c208-792e-8a01-3e6cfc34783f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VestingDomain_019d3360-c208-79fe-bceb-c5d827e6bb79" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_VestingDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_VestingAxis_019d3360-c208-792e-8a01-3e6cfc34783f" xlink:to="loc_us-gaap_VestingDomain_019d3360-c208-79fe-bceb-c5d827e6bb79" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationAwardTrancheTwoMember_019d3360-c208-79ec-9860-6a1023a509a8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationAwardTrancheTwoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VestingDomain_019d3360-c208-79fe-bceb-c5d827e6bb79" xlink:to="loc_us-gaap_ShareBasedCompensationAwardTrancheTwoMember_019d3360-c208-79ec-9860-6a1023a509a8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationAwardTrancheOneMember_019d3360-c208-7f88-952d-72d4b30cf5b7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationAwardTrancheOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VestingDomain_019d3360-c208-79fe-bceb-c5d827e6bb79" xlink:to="loc_us-gaap_ShareBasedCompensationAwardTrancheOneMember_019d3360-c208-7f88-952d-72d4b30cf5b7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationAwardTrancheThreeMember_019d3360-c208-7971-ad78-f3da27de8010" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationAwardTrancheThreeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VestingDomain_019d3360-c208-79fe-bceb-c5d827e6bb79" xlink:to="loc_us-gaap_ShareBasedCompensationAwardTrancheThreeMember_019d3360-c208-7971-ad78-f3da27de8010" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ShareBasedCompensationAwardTrancheFourMember_019d3360-c208-7149-b24b-e7e58558d33c" xlink:href="sdgr-20260331.xsd#sdgr_ShareBasedCompensationAwardTrancheFourMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VestingDomain_019d3360-c208-79fe-bceb-c5d827e6bb79" xlink:to="loc_sdgr_ShareBasedCompensationAwardTrancheFourMember_019d3360-c208-7149-b24b-e7e58558d33c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardDateAxis_019d3360-e7b1-7794-96e5-b9a1acc5d0d3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardDateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cd38a-fdd9-7be2-beec-d05c96d68fd1" xlink:to="loc_us-gaap_AwardDateAxis_019d3360-e7b1-7794-96e5-b9a1acc5d0d3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardDateDomain_019d3360-e7b1-7794-96e5-b9a1acc5d0d3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardDateDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardDateAxis_019d3360-e7b1-7794-96e5-b9a1acc5d0d3" xlink:to="loc_us-gaap_AwardDateDomain_019d3360-e7b1-7794-96e5-b9a1acc5d0d3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardDateDomain_019d3360-e7b1-7f8a-8c0c-ae08c8343481" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AwardDateDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardDateAxis_019d3360-e7b1-7794-96e5-b9a1acc5d0d3" xlink:to="loc_us-gaap_AwardDateDomain_019d3360-e7b1-7f8a-8c0c-ae08c8343481" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_March2025AwardMember_019d3360-e7b1-739a-95bc-9351a150e712" xlink:href="sdgr-20260331.xsd#sdgr_March2025AwardMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AwardDateDomain_019d3360-e7b1-7f8a-8c0c-ae08c8343481" xlink:to="loc_sdgr_March2025AwardMember_019d3360-e7b1-739a-95bc-9351a150e712" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_March2024AwardMember_019d3360-e7b1-72d0-abe2-51cc81d23676" xlink:href="sdgr-20260331.xsd#sdgr_March2024AwardMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AwardDateDomain_019d3360-e7b1-7f8a-8c0c-ae08c8343481" xlink:to="loc_sdgr_March2024AwardMember_019d3360-e7b1-72d0-abe2-51cc81d23676" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_February2023AwardMember_019d3360-e7b1-71bf-bad9-9b537754efc2" xlink:href="sdgr-20260331.xsd#sdgr_February2023AwardMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AwardDateDomain_019d3360-e7b1-7f8a-8c0c-ae08c8343481" xlink:to="loc_sdgr_February2023AwardMember_019d3360-e7b1-71bf-bad9-9b537754efc2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019d3361-1543-7d06-af6e-12f63a0b8015" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cd38a-fdd9-7be2-beec-d05c96d68fd1" xlink:to="loc_srt_RangeAxis_019d3361-1543-7d06-af6e-12f63a0b8015" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019d3361-1543-7d06-af6e-12f63a0b8015_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019d3361-1543-7d06-af6e-12f63a0b8015" xlink:to="loc_srt_RangeMember_019d3361-1543-7d06-af6e-12f63a0b8015_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019d3361-1543-79d0-995d-599e06961008" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019d3361-1543-7d06-af6e-12f63a0b8015" xlink:to="loc_srt_RangeMember_019d3361-1543-79d0-995d-599e06961008" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_019d3361-1543-7e88-9ad7-177236263a7a" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019d3361-1543-79d0-995d-599e06961008" xlink:to="loc_srt_MaximumMember_019d3361-1543-7e88-9ad7-177236263a7a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_019d3360-a6a0-7327-83b4-b1569f4a3b98" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_019d3360-a6a0-7327-83b4-b1569f4a3b98" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAwardConversionUponAchievementNumberOfSharesPerAward_019d3360-c208-7d48-a592-3a40bf3c90d6" xlink:href="sdgr-20260331.xsd#sdgr_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAwardConversionUponAchievementNumberOfSharesPerAward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_sdgr_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAwardConversionUponAchievementNumberOfSharesPerAward_019d3360-c208-7d48-a592-3a40bf3c90d6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_019d3360-c208-7d95-8f6f-e36df335246b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_019d3360-c208-7d95-8f6f-e36df335246b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_019d3360-c208-73f5-bb8c-aad214473f6d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_019d3360-c208-73f5-bb8c-aad214473f6d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019d3360-c208-786d-8be0-ecb4978d2652" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019d3360-c208-786d-8be0-ecb4978d2652" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019d3360-c208-712a-b9ef-e42e2a54e4fb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019d3360-c208-712a-b9ef-e42e2a54e4fb" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_019d3360-c208-734d-a9b4-d80e3b440964" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_019d3360-c208-734d-a9b4-d80e3b440964" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019d3360-c208-74b7-8a04-bca23401ee41" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019d3360-c208-74b7-8a04-bca23401ee41" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019d3360-e7b1-7e9c-b765-a3de405cc574" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_019d3360-e7b1-7e9c-b765-a3de405cc574" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue_019d3360-e7b1-7446-ae94-d4a1395725d1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodTotalFairValue_019d3360-e7b1-7446-ae94-d4a1395725d1" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAchievementPercent_019d3360-e7b1-76e6-9521-802fc30242ed" xlink:href="sdgr-20260331.xsd#sdgr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAchievementPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_sdgr_ShareBasedCompensationArrangementByShareBasedPaymentAwardAchievementPercent_019d3360-e7b1-76e6-9521-802fc30242ed" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_019d3360-e7b1-725c-a10a-464b07f5dcb7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_019d3360-e7b1-725c-a10a-464b07f5dcb7" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsEligibleToVestNumber_019d3360-e7b1-7e39-a012-8f35cab5d1d3" xlink:href="sdgr-20260331.xsd#sdgr_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsEligibleToVestNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_sdgr_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsEligibleToVestNumber_019d3360-e7b1-7e39-a012-8f35cab5d1d3" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_MaximumPercentageOfStockOptionsMustBeGrantedAtExercisePriceOfFairMarketValue_019d3361-1543-7b70-b31c-edc66e69e588" xlink:href="sdgr-20260331.xsd#sdgr_MaximumPercentageOfStockOptionsMustBeGrantedAtExercisePriceOfFairMarketValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_sdgr_MaximumPercentageOfStockOptionsMustBeGrantedAtExercisePriceOfFairMarketValue_019d3361-1543-7b70-b31c-edc66e69e588" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_019d3361-1543-71eb-b88b-5cf3128ed8cc" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_019d3361-1543-71eb-b88b-5cf3128ed8cc" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_019d3361-1543-74ba-818a-99cd7445d1aa" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_019d3361-1543-74ba-818a-99cd7445d1aa" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_019d3361-1543-778e-b327-cd77e6e05249" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_019d3361-1543-778e-b327-cd77e6e05249" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019d3361-1543-7611-8ee7-6fdceae0a1d5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019d3361-1543-7611-8ee7-6fdceae0a1d5" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockOptionsExercised_019d3361-1543-7697-86bd-88a20b9520d5" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProceedsFromStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ProceedsFromStockOptionsExercised_019d3361-1543-7697-86bd-88a20b9520d5" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019d3361-32fc-715d-9352-d32791ccd9cb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019d3361-32fc-715d-9352-d32791ccd9cb" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_019d3361-32fc-77f4-afbc-1ae7afe6c93a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_019d3361-32fc-77f4-afbc-1ae7afe6c93a" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_019d3361-523d-7379-be48-09fe08dcb9ca" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_019d3361-523d-7379-be48-09fe08dcb9ca" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestExercisableWeightedAverageRemainingContractualTerm1_019d3361-523d-7471-af43-9d6e6ab9ec7d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestExercisableWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestExercisableWeightedAverageRemainingContractualTerm1_019d3361-523d-7471-af43-9d6e6ab9ec7d" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1_019d3361-523d-73d7-930e-24a343b799b3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019d3360-a6a0-7505-9217-1bd715c23e70" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1_019d3361-523d-73d7-930e-24a343b799b3" xlink:type="arc" order="23"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/StockBasedCompensationSummaryofClassificationofStockBasedCompensationExpenseDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#StockBasedCompensationSummaryofClassificationofStockBasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/StockBasedCompensationSummaryofClassificationofStockBasedCompensationExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019cd38a-fdd9-77d0-80f1-17b8716c7fb2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cd38a-fdd9-75f1-b8d7-7c5691489dc1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019cd38a-fdd9-77d0-80f1-17b8716c7fb2" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cd38a-fdd9-75f1-b8d7-7c5691489dc1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_019cd38a-fdd9-74a5-aa02-0760f708dda3" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_019cd38a-fdd9-75f1-b8d7-7c5691489dc1" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_019cd38a-fdd9-74a5-aa02-0760f708dda3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_019cd38a-fdd9-74a5-aa02-0760f708dda3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_019cd38a-fdd9-74a5-aa02-0760f708dda3" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_019cd38a-fdd9-74a5-aa02-0760f708dda3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_019cd38a-fdd9-7e33-be16-70b5afeadb34" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_019cd38a-fdd9-74a5-aa02-0760f708dda3" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_019cd38a-fdd9-7e33-be16-70b5afeadb34" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfSalesMember_019cd38a-fdd9-7a2e-89d4-837fe79dec15" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostOfSalesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_019cd38a-fdd9-7e33-be16-70b5afeadb34" xlink:to="loc_us-gaap_CostOfSalesMember_019cd38a-fdd9-7a2e-89d4-837fe79dec15" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_019cd38a-fdd9-743e-ba5b-f3c76600422e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_019cd38a-fdd9-7e33-be16-70b5afeadb34" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_019cd38a-fdd9-743e-ba5b-f3c76600422e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingAndMarketingExpenseMember_019cd38a-fdd9-7e50-b358-14f871cff9d1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SellingAndMarketingExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_019cd38a-fdd9-7e33-be16-70b5afeadb34" xlink:to="loc_us-gaap_SellingAndMarketingExpenseMember_019cd38a-fdd9-7e50-b358-14f871cff9d1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpenseMember_019cd38a-fdd9-7604-af60-ea951b5e7e83" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_019cd38a-fdd9-7e33-be16-70b5afeadb34" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpenseMember_019cd38a-fdd9-7604-af60-ea951b5e7e83" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_019cd38a-fdd9-7cea-8161-d4b69b77b033" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_019cd38a-fdd9-77d0-80f1-17b8716c7fb2" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_019cd38a-fdd9-7cea-8161-d4b69b77b033" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/NetLossperShareAttributabletoCommonandLimitedCommonStockholdersScheduleofPotentiallyDilutiveSecuritiesnotIncludedinDilutedPerShareCalculationsAntidilutiveDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#NetLossperShareAttributabletoCommonandLimitedCommonStockholdersScheduleofPotentiallyDilutiveSecuritiesnotIncludedinDilutedPerShareCalculationsAntidilutiveDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/NetLossperShareAttributabletoCommonandLimitedCommonStockholdersScheduleofPotentiallyDilutiveSecuritiesnotIncludedinDilutedPerShareCalculationsAntidilutiveDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019cd38a-fdd9-7213-9c67-9b0d1d0b8bd7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019cd38a-fdd9-7471-85b3-338f4c97dfc6" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019cd38a-fdd9-7213-9c67-9b0d1d0b8bd7" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019cd38a-fdd9-7471-85b3-338f4c97dfc6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019cd38a-fdd9-7e21-a263-99ca66f7f24c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019cd38a-fdd9-7471-85b3-338f4c97dfc6" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019cd38a-fdd9-7e21-a263-99ca66f7f24c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cd38a-fdd9-7e21-a263-99ca66f7f24c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019cd38a-fdd9-7e21-a263-99ca66f7f24c" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cd38a-fdd9-7e21-a263-99ca66f7f24c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cd38a-fdd9-728d-a315-3ef5c377bd86" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019cd38a-fdd9-7e21-a263-99ca66f7f24c" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cd38a-fdd9-728d-a315-3ef5c377bd86" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_019d20b2-1059-7c14-b822-5cf479eedd11" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cd38a-fdd9-728d-a315-3ef5c377bd86" xlink:to="loc_us-gaap_EmployeeStockOptionMember_019d20b2-1059-7c14-b822-5cf479eedd11" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockCompensationPlanMember_019d20b2-1059-79f3-b3c0-a9801b72b360" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockCompensationPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019cd38a-fdd9-728d-a315-3ef5c377bd86" xlink:to="loc_us-gaap_StockCompensationPlanMember_019d20b2-1059-79f3-b3c0-a9801b72b360" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_019cd38a-fdd9-7503-91a0-b2ca882053f1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019cd38a-fdd9-7213-9c67-9b0d1d0b8bd7" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_019cd38a-fdd9-7503-91a0-b2ca882053f1" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/EquityInvestmentsDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#EquityInvestmentsDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/EquityInvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEquityMethodInvestmentsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEquityMethodInvestmentsTable_019cd38a-fdd9-7890-9284-c18a1fa5eae1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfEquityMethodInvestmentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_us-gaap_ScheduleOfEquityMethodInvestmentsTable_019cd38a-fdd9-7890-9284-c18a1fa5eae1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_019d20c0-c39a-73f6-82bf-94245a1df0ef" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsTable_019cd38a-fdd9-7890-9284-c18a1fa5eae1" xlink:to="loc_us-gaap_FinancialInstrumentAxis_019d20c0-c39a-73f6-82bf-94245a1df0ef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019d20c0-c39a-73f6-82bf-94245a1df0ef_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019d20c0-c39a-73f6-82bf-94245a1df0ef" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019d20c0-c39a-73f6-82bf-94245a1df0ef_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019d20c0-c39a-7329-81cd-bb0cfba305c8" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019d20c0-c39a-73f6-82bf-94245a1df0ef" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019d20c0-c39a-7329-81cd-bb0cfba305c8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_NimbusTherapeuticsLLCMember_019d20c0-c39a-7449-add5-cad6aa7c7496" xlink:href="sdgr-20260331.xsd#sdgr_NimbusTherapeuticsLLCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019d20c0-c39a-7329-81cd-bb0cfba305c8" xlink:to="loc_sdgr_NimbusTherapeuticsLLCMember_019d20c0-c39a-7449-add5-cad6aa7c7496" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_AjaxTherapeuticsIncMember_019d20c0-c39a-7c63-bd73-97359ff6d58a" xlink:href="sdgr-20260331.xsd#sdgr_AjaxTherapeuticsIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019d20c0-c39a-7329-81cd-bb0cfba305c8" xlink:to="loc_sdgr_AjaxTherapeuticsIncMember_019d20c0-c39a-7c63-bd73-97359ff6d58a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_StructureTherapeuticsMember_019d20c0-f722-76b2-81b2-883f3d1e1efb" xlink:href="sdgr-20260331.xsd#sdgr_StructureTherapeuticsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019d20c0-c39a-7329-81cd-bb0cfba305c8" xlink:to="loc_sdgr_StructureTherapeuticsMember_019d20c0-f722-76b2-81b2-883f3d1e1efb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019d20c0-c39a-7bbf-8598-89f78449f985" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsTable_019cd38a-fdd9-7890-9284-c18a1fa5eae1" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019d20c0-c39a-7bbf-8598-89f78449f985" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019d20c0-c39a-7bbf-8598-89f78449f985_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019d20c0-c39a-7bbf-8598-89f78449f985" xlink:to="loc_us-gaap_ClassOfStockDomain_019d20c0-c39a-7bbf-8598-89f78449f985_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019d20c0-c39a-774a-b08e-136f4323fe03" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019d20c0-c39a-7bbf-8598-89f78449f985" xlink:to="loc_us-gaap_ClassOfStockDomain_019d20c0-c39a-774a-b08e-136f4323fe03" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesBPreferredStockMember_019d20c0-c39a-7090-b0a3-4f28833a5b8d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SeriesBPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019d20c0-c39a-774a-b08e-136f4323fe03" xlink:to="loc_us-gaap_SeriesBPreferredStockMember_019d20c0-c39a-7090-b0a3-4f28833a5b8d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeriesCPreferredStockMember_019d20c0-c39a-702d-b8e6-00d0ac48ff7e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SeriesCPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019d20c0-c39a-774a-b08e-136f4323fe03" xlink:to="loc_us-gaap_SeriesCPreferredStockMember_019d20c0-c39a-702d-b8e6-00d0ac48ff7e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AdrMember_019d20c0-f722-7ecd-b757-722ea72919b4" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_AdrMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019d20c0-c39a-774a-b08e-136f4323fe03" xlink:to="loc_dei_AdrMember_019d20c0-f722-7ecd-b757-722ea72919b4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_019d20c0-f722-79a5-8261-3580baccf954" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsTable_019cd38a-fdd9-7890-9284-c18a1fa5eae1" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_019d20c0-f722-79a5-8261-3580baccf954" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_019d20c0-f722-79a5-8261-3580baccf954_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_019d20c0-f722-79a5-8261-3580baccf954" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_019d20c0-f722-79a5-8261-3580baccf954_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_019d20c0-f722-70b3-b8e5-b06acaafccfd" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_019d20c0-f722-79a5-8261-3580baccf954" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_019d20c0-f722-70b3-b8e5-b06acaafccfd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_StructureTherapeuticsMember_019d20c0-f722-7466-bb94-811b407bb7cb" xlink:href="sdgr-20260331.xsd#sdgr_StructureTherapeuticsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_019d20c0-f722-70b3-b8e5-b06acaafccfd" xlink:to="loc_sdgr_StructureTherapeuticsMember_019d20c0-f722-7466-bb94-811b407bb7cb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesWithoutReadilyDeterminableFairValueAmount_019d20c0-c39a-7b08-a6f2-0c07c375530c" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquitySecuritiesWithoutReadilyDeterminableFairValueAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_us-gaap_EquitySecuritiesWithoutReadilyDeterminableFairValueAmount_019d20c0-c39a-7b08-a6f2-0c07c375530c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_NumberOfPreferredSharesPurchased_019d20c0-c39a-73ee-b67a-458b7646a7fa" xlink:href="sdgr-20260331.xsd#sdgr_NumberOfPreferredSharesPurchased"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_sdgr_NumberOfPreferredSharesPurchased_019d20c0-c39a-73ee-b67a-458b7646a7fa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireEquitySecuritiesFvNi_019d20c0-f722-7c7d-924d-5396ce4f4dd2" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PaymentsToAcquireEquitySecuritiesFvNi"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_us-gaap_PaymentsToAcquireEquitySecuritiesFvNi_019d20c0-f722-7c7d-924d-5396ce4f4dd2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockConvertibleConversionRatio_019d20c0-f722-7a19-b90c-bb9af05c064f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_PreferredStockConvertibleConversionRatio"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_us-gaap_PreferredStockConvertibleConversionRatio_019d20c0-f722-7a19-b90c-bb9af05c064f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_NumberOfSharesPurchased_019d20c0-f722-7b63-a600-7d951d47d63b" xlink:href="sdgr-20260331.xsd#sdgr_NumberOfSharesPurchased"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_sdgr_NumberOfSharesPurchased_019d20c0-f722-7b63-a600-7d951d47d63b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_AmericanDepositorySharesPurchasedPricePerShare_019d20c0-f722-7908-b0c5-3d7e5189e87e" xlink:href="sdgr-20260331.xsd#sdgr_AmericanDepositorySharesPurchasedPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_sdgr_AmericanDepositorySharesPurchasedPricePerShare_019d20c0-f722-7908-b0c5-3d7e5189e87e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityNoteStockSplitConversionRatio1_019d20c0-f722-78cd-ba97-1cbb9c237ba9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StockholdersEquityNoteStockSplitConversionRatio1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_us-gaap_StockholdersEquityNoteStockSplitConversionRatio1_019d20c0-f722-78cd-ba97-1cbb9c237ba9" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleOfEquitySecuritiesFvNi_019d20c0-f722-76f0-a49a-705be108af03" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProceedsFromSaleOfEquitySecuritiesFvNi"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_us-gaap_ProceedsFromSaleOfEquitySecuritiesFvNi_019d20c0-f722-76f0-a49a-705be108af03" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNiGainLoss_019d20c0-f722-74c6-beb8-c36a4f0a6e09" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquitySecuritiesFvNiGainLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_us-gaap_EquitySecuritiesFvNiGainLoss_019d20c0-f722-74c6-beb8-c36a4f0a6e09" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNi_019d20c0-f722-7cc6-ab0a-56202075ac4d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquitySecuritiesFvNi"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfEquityMethodInvestmentsLineItems_019d20c0-c39a-7116-a2e8-31768aeee54b" xlink:to="loc_us-gaap_EquitySecuritiesFvNi_019d20c0-f722-7cc6-ab0a-56202075ac4d" xlink:type="arc" order="9"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/RelatedPartyTransactionsDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#RelatedPartyTransactionsDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/RelatedPartyTransactionsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionLineItems_019d20c6-036d-772f-aa25-fd64924140c7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyTransactionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_019cd38a-fdd9-7c2e-961e-7bca7a84ea1a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_019d20c6-036d-772f-aa25-fd64924140c7" xlink:to="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_019cd38a-fdd9-7c2e-961e-7bca7a84ea1a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019d20c6-036d-7294-8134-dfd874471765" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_019cd38a-fdd9-7c2e-961e-7bca7a84ea1a" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019d20c6-036d-7294-8134-dfd874471765" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019d20c6-036d-7294-8134-dfd874471765_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019d20c6-036d-7294-8134-dfd874471765" xlink:to="loc_us-gaap_RelatedPartyDomain_019d20c6-036d-7294-8134-dfd874471765_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019d20c6-036d-7b05-801a-3a2cba2aa9f7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019d20c6-036d-7294-8134-dfd874471765" xlink:to="loc_us-gaap_RelatedPartyDomain_019d20c6-036d-7b05-801a-3a2cba2aa9f7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_DirectorMember_019d20c6-036d-72ae-91ea-aaee31c34b83" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_DirectorMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_019d20c6-036d-7b05-801a-3a2cba2aa9f7" xlink:to="loc_srt_DirectorMember_019d20c6-036d-72ae-91ea-aaee31c34b83" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyMember_019d20c6-036d-7cec-a424-e0e4182e661e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_019d20c6-036d-7b05-801a-3a2cba2aa9f7" xlink:to="loc_us-gaap_RelatedPartyMember_019d20c6-036d-7cec-a424-e0e4182e661e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_019d20c6-036d-7ffd-a70d-9d2c4d656044" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_019cd38a-fdd9-7c2e-961e-7bca7a84ea1a" xlink:to="loc_srt_CounterpartyNameAxis_019d20c6-036d-7ffd-a70d-9d2c4d656044" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d20c6-036d-7ffd-a70d-9d2c4d656044_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_019d20c6-036d-7ffd-a70d-9d2c4d656044" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d20c6-036d-7ffd-a70d-9d2c4d656044_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d20c6-036d-723a-88a5-73569894a156" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_019d20c6-036d-7ffd-a70d-9d2c4d656044" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d20c6-036d-723a-88a5-73569894a156" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_BillAndMelindaGatesFoundationTrustMember_019d20c6-036d-76bc-b47c-962010dc191f" xlink:href="sdgr-20260331.xsd#sdgr_BillAndMelindaGatesFoundationTrustMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d20c6-036d-723a-88a5-73569894a156" xlink:to="loc_sdgr_BillAndMelindaGatesFoundationTrustMember_019d20c6-036d-76bc-b47c-962010dc191f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_GatesVenturesLLCMember_019d20c6-036d-764c-9abf-65001a09e761" xlink:href="sdgr-20260331.xsd#sdgr_GatesVenturesLLCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d20c6-036d-723a-88a5-73569894a156" xlink:to="loc_sdgr_GatesVenturesLLCMember_019d20c6-036d-764c-9abf-65001a09e761" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ColumbiaUniversityAndRichardFriesnerMember_019d20c6-2371-7065-bc46-1006b7b7039d" xlink:href="sdgr-20260331.xsd#sdgr_ColumbiaUniversityAndRichardFriesnerMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019d20c6-036d-723a-88a5-73569894a156" xlink:to="loc_sdgr_ColumbiaUniversityAndRichardFriesnerMember_019d20c6-2371-7065-bc46-1006b7b7039d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_019d20c6-036d-7036-9c3d-cfc2af3e15c5" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_019cd38a-fdd9-7c2e-961e-7bca7a84ea1a" xlink:to="loc_srt_ProductOrServiceAxis_019d20c6-036d-7036-9c3d-cfc2af3e15c5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019d20c6-036d-7036-9c3d-cfc2af3e15c5_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_019d20c6-036d-7036-9c3d-cfc2af3e15c5" xlink:to="loc_srt_ProductsAndServicesDomain_019d20c6-036d-7036-9c3d-cfc2af3e15c5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_019d20c6-036d-78f0-9e8c-9110f77ae8af" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_019d20c6-036d-7036-9c3d-cfc2af3e15c5" xlink:to="loc_srt_ProductsAndServicesDomain_019d20c6-036d-78f0-9e8c-9110f77ae8af" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_ContributionMember_019d20c6-036d-7124-b148-ec76c68f2f54" xlink:href="sdgr-20260331.xsd#sdgr_ContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019d20c6-036d-78f0-9e8c-9110f77ae8af" xlink:to="loc_sdgr_ContributionMember_019d20c6-036d-7124-b148-ec76c68f2f54" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareContributionMember_019d20c6-036d-7ea4-ae37-52e9588889a6" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareContributionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_019d20c6-036d-78f0-9e8c-9110f77ae8af" xlink:to="loc_sdgr_SoftwareContributionMember_019d20c6-036d-7ea4-ae37-52e9588889a6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019d20c6-036d-70d6-a5b0-79dc20dd10ef" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_019cd38a-fdd9-7c2e-961e-7bca7a84ea1a" xlink:to="loc_srt_RangeAxis_019d20c6-036d-70d6-a5b0-79dc20dd10ef" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019d20c6-036d-70d6-a5b0-79dc20dd10ef_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019d20c6-036d-70d6-a5b0-79dc20dd10ef" xlink:to="loc_srt_RangeMember_019d20c6-036d-70d6-a5b0-79dc20dd10ef_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019d20c6-036d-7b45-bb7e-d2829d292f64" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019d20c6-036d-70d6-a5b0-79dc20dd10ef" xlink:to="loc_srt_RangeMember_019d20c6-036d-7b45-bb7e-d2829d292f64" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_019d20c6-036d-7684-a60f-9af3a062e47c" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019d20c6-036d-7b45-bb7e-d2829d292f64" xlink:to="loc_srt_MinimumMember_019d20c6-036d-7684-a60f-9af3a062e47c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_019d20c6-036d-79e0-9ac2-90fd53c9cf6e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRelatedPartyTransactionsByRelatedPartyTable_019cd38a-fdd9-7c2e-961e-7bca7a84ea1a" xlink:to="loc_us-gaap_TypeOfArrangementAxis_019d20c6-036d-79e0-9ac2-90fd53c9cf6e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d20c6-036d-79e0-9ac2-90fd53c9cf6e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019d20c6-036d-79e0-9ac2-90fd53c9cf6e" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d20c6-036d-79e0-9ac2-90fd53c9cf6e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d20c6-036d-7628-8479-904b9dc09223" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_019d20c6-036d-79e0-9ac2-90fd53c9cf6e" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d20c6-036d-7628-8479-904b9dc09223" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_AgreementWithGatesVenturesLimitedLiabilityCompanyMember_019d20c6-036d-7b7e-a806-57a89b4ec5dd" xlink:href="sdgr-20260331.xsd#sdgr_AgreementWithGatesVenturesLimitedLiabilityCompanyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_019d20c6-036d-7628-8479-904b9dc09223" xlink:to="loc_sdgr_AgreementWithGatesVenturesLimitedLiabilityCompanyMember_019d20c6-036d-7b7e-a806-57a89b4ec5dd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionAmountsOfTransaction_019d20c6-036d-7920-a4c9-b06fabb9c7d0" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RelatedPartyTransactionAmountsOfTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_019d20c6-036d-772f-aa25-fd64924140c7" xlink:to="loc_us-gaap_RelatedPartyTransactionAmountsOfTransaction_019d20c6-036d-7920-a4c9-b06fabb9c7d0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019d20c6-036d-7334-a538-24fa38c1c739" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_019d20c6-036d-772f-aa25-fd64924140c7" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019d20c6-036d-7334-a538-24fa38c1c739" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueNotFromContractWithCustomer_019d20c6-036d-75a6-8fdc-c4c56e707835" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueNotFromContractWithCustomer"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_019d20c6-036d-772f-aa25-fd64924140c7" xlink:to="loc_us-gaap_RevenueNotFromContractWithCustomer_019d20c6-036d-75a6-8fdc-c4c56e707835" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashCurrent_019d20c6-036d-779e-b17f-8833cfb26b2a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RestrictedCashCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_019d20c6-036d-772f-aa25-fd64924140c7" xlink:to="loc_us-gaap_RestrictedCashCurrent_019d20c6-036d-779e-b17f-8833cfb26b2a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareContributionRevenueRecognized_019d20c6-036d-7315-b63d-529c7fade3cd" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareContributionRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_019d20c6-036d-772f-aa25-fd64924140c7" xlink:to="loc_sdgr_SoftwareContributionRevenueRecognized_019d20c6-036d-7315-b63d-529c7fade3cd" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_019d20c6-036d-77ce-9407-93839f88fa81" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_019d20c6-036d-772f-aa25-fd64924140c7" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_019d20c6-036d-77ce-9407-93839f88fa81" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_PercentageOfVotingSecurities_019d20c6-036d-78c9-8339-f0537e9042f6" xlink:href="sdgr-20260331.xsd#sdgr_PercentageOfVotingSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_019d20c6-036d-772f-aa25-fd64924140c7" xlink:to="loc_sdgr_PercentageOfVotingSecurities_019d20c6-036d-78c9-8339-f0537e9042f6" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareContributionRevenueRecognitionAmount_019d20c6-036d-7f5f-b95f-3be923c0fce6" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareContributionRevenueRecognitionAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyTransactionLineItems_019d20c6-036d-772f-aa25-fd64924140c7" xlink:to="loc_sdgr_SoftwareContributionRevenueRecognitionAmount_019d20c6-036d-7f5f-b95f-3be923c0fce6" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/SegmentReportingSummaryofFinancialInformationwithRespecttoReportableSegmentsDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#SegmentReportingSummaryofFinancialInformationwithRespecttoReportableSegmentsDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/SegmentReportingSummaryofFinancialInformationwithRespecttoReportableSegmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_019cd38a-fdd9-7d51-9b28-25eda214851f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019cd38a-fdd9-7f75-a82b-2a14c5ae0795" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cd38a-fdd9-7d51-9b28-25eda214851f" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019cd38a-fdd9-7f75-a82b-2a14c5ae0795" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_019cd38a-fdd9-7603-ab5f-a81771e2ad30" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019cd38a-fdd9-7f75-a82b-2a14c5ae0795" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_019cd38a-fdd9-7603-ab5f-a81771e2ad30" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_019cd38a-fdd9-7603-ab5f-a81771e2ad30_default" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_019cd38a-fdd9-7603-ab5f-a81771e2ad30" xlink:to="loc_us-gaap_SegmentDomain_019cd38a-fdd9-7603-ab5f-a81771e2ad30_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_019cd38a-fdd9-7713-b143-b91877259b29" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_019cd38a-fdd9-7603-ab5f-a81771e2ad30" xlink:to="loc_us-gaap_SegmentDomain_019cd38a-fdd9-7713-b143-b91877259b29" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_SoftwareSegmentMember_019cd38a-fdd9-7469-b1ba-8fe2dbe1b0dc" xlink:href="sdgr-20260331.xsd#sdgr_SoftwareSegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_019cd38a-fdd9-7713-b143-b91877259b29" xlink:to="loc_sdgr_SoftwareSegmentMember_019cd38a-fdd9-7469-b1ba-8fe2dbe1b0dc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_DrugDiscoverySegmentMember_019cd38a-fdd9-79e0-b5c0-8c465cbd07b1" xlink:href="sdgr-20260331.xsd#sdgr_DrugDiscoverySegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_019cd38a-fdd9-7713-b143-b91877259b29" xlink:to="loc_sdgr_DrugDiscoverySegmentMember_019cd38a-fdd9-79e0-b5c0-8c465cbd07b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationRevenueAbstract_019cd38a-fdd9-72eb-ae16-57661bf2339f" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SegmentReportingInformationRevenueAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cd38a-fdd9-7d51-9b28-25eda214851f" xlink:to="loc_us-gaap_SegmentReportingInformationRevenueAbstract_019cd38a-fdd9-72eb-ae16-57661bf2339f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019cd38a-fdd9-7140-80f1-72ef5e3d02b7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationRevenueAbstract_019cd38a-fdd9-72eb-ae16-57661bf2339f" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019cd38a-fdd9-7140-80f1-72ef5e3d02b7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfRevenueAbstract_019cd38a-fdd9-7a82-b252-e489339fb122" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostOfRevenueAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cd38a-fdd9-7d51-9b28-25eda214851f" xlink:to="loc_us-gaap_CostOfRevenueAbstract_019cd38a-fdd9-7a82-b252-e489339fb122" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfRevenue_019cd38a-fdd9-7310-a8d4-8b5105b5978d" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_CostOfRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostOfRevenueAbstract_019cd38a-fdd9-7a82-b252-e489339fb122" xlink:to="loc_us-gaap_CostOfRevenue_019cd38a-fdd9-7310-a8d4-8b5105b5978d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GrossProfitAbstract_019cd38a-fdd9-7fa2-99b1-de438b6deb05" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GrossProfitAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cd38a-fdd9-7d51-9b28-25eda214851f" xlink:to="loc_us-gaap_GrossProfitAbstract_019cd38a-fdd9-7fa2-99b1-de438b6deb05" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GrossProfit_019cd38a-fdd9-7160-a3c7-38c6c8f30a50" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GrossProfit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_GrossProfitAbstract_019cd38a-fdd9-7fa2-99b1-de438b6deb05" xlink:to="loc_us-gaap_GrossProfit_019cd38a-fdd9-7160-a3c7-38c6c8f30a50" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_UnallocatedAbstract_019cd38a-fdd9-7045-879f-8b9a0bf2865d" xlink:href="sdgr-20260331.xsd#sdgr_UnallocatedAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cd38a-fdd9-7d51-9b28-25eda214851f" xlink:to="loc_sdgr_UnallocatedAbstract_019cd38a-fdd9-7045-879f-8b9a0bf2865d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_019cd38a-fdd9-7819-bcf3-46a88fce1345" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_sdgr_UnallocatedAbstract_019cd38a-fdd9-7045-879f-8b9a0bf2865d" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_019cd38a-fdd9-7819-bcf3-46a88fce1345" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingAndMarketingExpense_019cd38a-fdd9-733f-9965-e3daca3715f1" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_SellingAndMarketingExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_sdgr_UnallocatedAbstract_019cd38a-fdd9-7045-879f-8b9a0bf2865d" xlink:to="loc_us-gaap_SellingAndMarketingExpense_019cd38a-fdd9-733f-9965-e3daca3715f1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_019cd38a-fdd9-7afd-a9fc-0445e711e2bb" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_sdgr_UnallocatedAbstract_019cd38a-fdd9-7045-879f-8b9a0bf2865d" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_019cd38a-fdd9-7afd-a9fc-0445e711e2bb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNiGainLoss_019cd38a-fdd9-7082-b8bc-f39df6c3ffd9" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EquitySecuritiesFvNiGainLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_sdgr_UnallocatedAbstract_019cd38a-fdd9-7045-879f-8b9a0bf2865d" xlink:to="loc_us-gaap_EquitySecuritiesFvNiGainLoss_019cd38a-fdd9-7082-b8bc-f39df6c3ffd9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_019cd38a-fdd9-7136-aa48-277ab06378ef" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_sdgr_UnallocatedAbstract_019cd38a-fdd9-7045-879f-8b9a0bf2865d" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_019cd38a-fdd9-7136-aa48-277ab06378ef" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_019cd38a-fdd9-77a9-a6b0-d7ac38cf436a" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_sdgr_UnallocatedAbstract_019cd38a-fdd9-7045-879f-8b9a0bf2865d" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_019cd38a-fdd9-77a9-a6b0-d7ac38cf436a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProfitLoss_019cd38a-fdd9-7d0b-8445-3f9533b162de" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ProfitLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019cd38a-fdd9-7d51-9b28-25eda214851f" xlink:to="loc_us-gaap_ProfitLoss_019cd38a-fdd9-7d0b-8445-3f9533b162de" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.schrodinger.com/role/SegmentReportingScheduleofRevenuesbyGeographicAreaDetails" xlink:type="simple" xlink:href="sdgr-20260331.xsd#SegmentReportingScheduleofRevenuesbyGeographicAreaDetails"/>
  <link:definitionLink xlink:role="http://www.schrodinger.com/role/SegmentReportingScheduleofRevenuesbyGeographicAreaDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems_019cd38a-fe86-7cbe-b668-4e159f97dfed" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable_019cd38a-fe85-77eb-8c19-c9f337072ed7" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems_019cd38a-fe86-7cbe-b668-4e159f97dfed" xlink:to="loc_us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable_019cd38a-fe85-77eb-8c19-c9f337072ed7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_019cd38a-fe86-7ebd-a75b-09c8c7e8b84c" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRevenuesFromExternalCustomersAndLongLivedAssetsTable_019cd38a-fe85-77eb-8c19-c9f337072ed7" xlink:to="loc_srt_StatementGeographicalAxis_019cd38a-fe86-7ebd-a75b-09c8c7e8b84c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019cd38a-fe86-7ebd-a75b-09c8c7e8b84c_default" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_019cd38a-fe86-7ebd-a75b-09c8c7e8b84c" xlink:to="loc_srt_SegmentGeographicalDomain_019cd38a-fe86-7ebd-a75b-09c8c7e8b84c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019cd38a-fe86-7577-9d3f-df3c516d12de" xlink:href="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_019cd38a-fe86-7ebd-a75b-09c8c7e8b84c" xlink:to="loc_srt_SegmentGeographicalDomain_019cd38a-fe86-7577-9d3f-df3c516d12de" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_country_US_019cd38a-fe86-7f0b-a814-041ccf7a46d8" xlink:href="https://xbrl.sec.gov/country/2025/country-2025.xsd#country_US"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019cd38a-fe86-7577-9d3f-df3c516d12de" xlink:to="loc_country_US_019cd38a-fe86-7f0b-a814-041ccf7a46d8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EMEAMember_019cd38a-fe86-726a-bfc1-ba852aa3bd8e" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_EMEAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019cd38a-fe86-7577-9d3f-df3c516d12de" xlink:to="loc_us-gaap_EMEAMember_019cd38a-fe86-726a-bfc1-ba852aa3bd8e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_sdgr_APACMember_019cd38a-fe86-7ffa-90f1-10d60e29103b" xlink:href="sdgr-20260331.xsd#sdgr_APACMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019cd38a-fe86-7577-9d3f-df3c516d12de" xlink:to="loc_sdgr_APACMember_019cd38a-fe86-7ffa-90f1-10d60e29103b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonUsMember_019cd38a-fe86-7d51-b5f7-a5966691c1d4" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_NonUsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019cd38a-fe86-7577-9d3f-df3c516d12de" xlink:to="loc_us-gaap_NonUsMember_019cd38a-fe86-7d51-b5f7-a5966691c1d4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019cd38a-fe86-7e6e-843d-7708faf50830" xlink:href="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesFromExternalCustomersAndLongLivedAssetsLineItems_019cd38a-fe86-7cbe-b668-4e159f97dfed" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_019cd38a-fe86-7e6e-843d-7708faf50830" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
