diff --git a/src/libraries/Microsoft.Extensions.DependencyInjection/src/ServiceLookup/CallSiteFactory.cs b/src/libraries/Microsoft.Extensions.DependencyInjection/src/ServiceLookup/CallSiteFactory.cs
index b64a8a9b9f7ba2..490337d14b028c 100644
--- a/src/libraries/Microsoft.Extensions.DependencyInjection/src/ServiceLookup/CallSiteFactory.cs
+++ b/src/libraries/Microsoft.Extensions.DependencyInjection/src/ServiceLookup/CallSiteFactory.cs
@@ -344,11 +344,21 @@ private static bool AreCompatible(DynamicallyAccessedMemberTypes serviceDynamica
                                 // For AnyKey, we want to cache based on descriptor identity, not AnyKey that cacheKey has.
                                 ServiceIdentifier registrationKey = isAnyKeyLookup ? ServiceIdentifier.FromDescriptor(_descriptors[i]) : cacheKey;
                                 slot = GetSlot(registrationKey);
-                                if (CreateOpenGeneric(_descriptors[i], registrationKey, callSiteChain, slot, throwOnConstraintViolation: false) is { } callSite)
+
+                                // We skip open generics with incompatible constraints.
+                                if (CreateOpenGeneric(_descriptors[i], registrationKey, callSiteChain, slot, false) is { } callSite)
                                 {
                                     AddCallSite(callSite, i);
                                     UpdateSlot(registrationKey);
                                 }
+                                else if (slot == 0)
+                                {
+                                    // If the last registration has incompatible constraints, we still need to update the slot.
+                                    // This ensures that single service resolution (GetService) will attempt to resolve using the last
+                                    // registration and throw an ArgumentException, maintaining "last wins" semantics. During enumerable
+                                    // resolution (GetServices), the incompatible registration is simply skipped.
+                                    UpdateSlot(registrationKey);
+                                }
                             }
                         }
                     }
diff --git a/src/libraries/Microsoft.Extensions.DependencyInjection/tests/DI.Tests/ServiceProviderContainerTests.cs b/src/libraries/Microsoft.Extensions.DependencyInjection/tests/DI.Tests/ServiceProviderContainerTests.cs
index 94802673078634..2e837783951f7f 100644
--- a/src/libraries/Microsoft.Extensions.DependencyInjection/tests/DI.Tests/ServiceProviderContainerTests.cs
+++ b/src/libraries/Microsoft.Extensions.DependencyInjection/tests/DI.Tests/ServiceProviderContainerTests.cs
@@ -1312,6 +1312,18 @@ public void ResolveKeyedServiceWithKeyedParameter_MissingRegistrationButWithUnke
             Assert.Contains("Microsoft.Extensions.DependencyInjection.Specification.KeyedDependencyInjectionSpecificationTests+IService", ex.ToString());
         }
 
+        [Fact]
+        public void InvalidConstrainedOpenGenericIsSkippedInEnumerableButThrowsInSingleResolution()
+        {
+            var sc = new ServiceCollection();
+            sc.AddSingleton(typeof(IBB<>), typeof(GenericBB<>));
+            sc.AddSingleton(typeof(IBB<>), typeof(ConstrainedGenericBB<>));
+            var sp = CreateServiceProvider(sc);
+
+            Assert.Single(sp.GetServices<IBB<IBB<string>>>());
+            Assert.Throws<ArgumentException>(() => sp.GetService<IBB<IBB<string>>>());
+        }
+
         private async Task<bool> ResolveUniqueServicesConcurrently()
         {
             var types = new Type[]