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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019c7bf5-43ba-73bf-b385-d51b42655d91,g:ab3782b0-6c98-433d-bcbc-f0380ecab343-->
<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.enterprisebank.com/role/DocumentandEntityInformationDocument" xlink:type="simple" xlink:href="efsc-20260428.xsd#DocumentandEntityInformationDocument"/>
  <link:definitionLink xlink:role="http://www.enterprisebank.com/role/DocumentandEntityInformationDocument" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" 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_019c7bf5-43ba-7b4a-9ed4-06a5caa8b8af" 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_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_us-gaap_StatementTable_019c7bf5-43ba-7b4a-9ed4-06a5caa8b8af" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019c7bf5-43ba-733d-9183-fd1b5be196b2" 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_019c7bf5-43ba-7b4a-9ed4-06a5caa8b8af" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019c7bf5-43ba-733d-9183-fd1b5be196b2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019c7bf5-43ba-733d-9183-fd1b5be196b2_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_019c7bf5-43ba-733d-9183-fd1b5be196b2" xlink:to="loc_us-gaap_ClassOfStockDomain_019c7bf5-43ba-733d-9183-fd1b5be196b2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019c7bf5-43ba-7a59-b4e0-cb13dce262a2" 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_019c7bf5-43ba-733d-9183-fd1b5be196b2" xlink:to="loc_us-gaap_ClassOfStockDomain_019c7bf5-43ba-7a59-b4e0-cb13dce262a2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_019c7bf5-43ba-7c96-9044-955ee42c228a" 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_019c7bf5-43ba-7a59-b4e0-cb13dce262a2" xlink:to="loc_us-gaap_CommonStockMember_019c7bf5-43ba-7c96-9044-955ee42c228a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_efsc_DepositarySharesMember_019c7bf5-43ba-746a-8a75-a7e1d5a84cd7" xlink:href="efsc-20260428.xsd#efsc_DepositarySharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019c7bf5-43ba-7a59-b4e0-cb13dce262a2" xlink:to="loc_efsc_DepositarySharesMember_019c7bf5-43ba-746a-8a75-a7e1d5a84cd7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentType_019c7bf5-43ba-73b7-9c9f-db310c4b20e3" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_DocumentType_019c7bf5-43ba-73b7-9c9f-db310c4b20e3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentPeriodEndDate_019c7bf5-43ba-7c7e-a303-6a741d006607" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_DocumentPeriodEndDate_019c7bf5-43ba-7c7e-a303-6a741d006607" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityRegistrantName_019c7bf5-43ba-7635-ac7f-631d0d5134dc" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_EntityRegistrantName_019c7bf5-43ba-7635-ac7f-631d0d5134dc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityIncorporationStateCountryCode_019c7bf5-43ba-79b9-b800-ad2f91828997" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_EntityIncorporationStateCountryCode_019c7bf5-43ba-79b9-b800-ad2f91828997" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFileNumber_019c7bf5-43ba-7a24-8e53-9be10899d1c8" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_EntityFileNumber_019c7bf5-43ba-7a24-8e53-9be10899d1c8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityTaxIdentificationNumber_019c7bf5-43ba-7e49-8a93-88a1ddc2aa83" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_EntityTaxIdentificationNumber_019c7bf5-43ba-7e49-8a93-88a1ddc2aa83" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressAddressLine1_019c7bf5-43ba-79f1-908b-5fea1f3679f5" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_EntityAddressAddressLine1_019c7bf5-43ba-79f1-908b-5fea1f3679f5" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressCityOrTown_019c7bf5-43ba-79ce-961e-706419b73210" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_EntityAddressCityOrTown_019c7bf5-43ba-79ce-961e-706419b73210" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressStateOrProvince_019c7bf5-43ba-7c47-b8af-f29e4f0058c6" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_EntityAddressStateOrProvince_019c7bf5-43ba-7c47-b8af-f29e4f0058c6" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressPostalZipCode_019c7bf5-43ba-7e7e-b1d6-12afc20399ae" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_EntityAddressPostalZipCode_019c7bf5-43ba-7e7e-b1d6-12afc20399ae" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CityAreaCode_019c7bf5-43ba-7b64-a7b2-746aa22af4c1" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_CityAreaCode_019c7bf5-43ba-7b64-a7b2-746aa22af4c1" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LocalPhoneNumber_019c7bf5-43ba-7b67-8542-0670822c8cb2" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_LocalPhoneNumber_019c7bf5-43ba-7b67-8542-0670822c8cb2" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_WrittenCommunications_019c7bf5-43ba-7f08-94c8-17487264e4e4" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_WrittenCommunications"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_WrittenCommunications_019c7bf5-43ba-7f08-94c8-17487264e4e4" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_SolicitingMaterial_019c7bf5-43ba-71ac-a470-bfb47da6c9f0" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_SolicitingMaterial"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_SolicitingMaterial_019c7bf5-43ba-71ac-a470-bfb47da6c9f0" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_PreCommencementTenderOffer_019c7bf5-43ba-71a2-a0c1-dbdc6f643fba" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_PreCommencementTenderOffer"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_PreCommencementTenderOffer_019c7bf5-43ba-71a2-a0c1-dbdc6f643fba" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_PreCommencementIssuerTenderOffer_019c7bf5-43ba-712e-8546-d4806edf6984" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_PreCommencementIssuerTenderOffer"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_PreCommencementIssuerTenderOffer_019c7bf5-43ba-712e-8546-d4806edf6984" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_Security12bTitle_019c7bf5-43ba-7ba0-83f6-db901a88fc25" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_Security12bTitle_019c7bf5-43ba-7ba0-83f6-db901a88fc25" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_TradingSymbol_019c7bf5-43ba-74be-a549-9e7d91fcab6e" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_TradingSymbol_019c7bf5-43ba-74be-a549-9e7d91fcab6e" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_SecurityExchangeName_019c7bf5-43ba-7d28-98fe-0722fbd00f7f" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_SecurityExchangeName_019c7bf5-43ba-7d28-98fe-0722fbd00f7f" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityEmergingGrowthCompany_019c7bf5-43ba-74ca-8ced-b877203ddba0" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_EntityEmergingGrowthCompany_019c7bf5-43ba-74ca-8ced-b877203ddba0" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCentralIndexKey_019c7bf5-43ba-72d4-a1f1-c8d4704d717f" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_EntityCentralIndexKey_019c7bf5-43ba-72d4-a1f1-c8d4704d717f" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AmendmentFlag_019c7bf5-43ba-71b2-89f2-70c549b7ec47" 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_us-gaap_StatementLineItems_019c7bf5-43ba-771a-88fb-babb04e6b9f2" xlink:to="loc_dei_AmendmentFlag_019c7bf5-43ba-71b2-89f2-70c549b7ec47" xlink:type="arc" order="21"/>
  </link:definitionLink>
</link:linkbase>