diff --git a/django/contrib/contenttypes/fields.py b/django/contrib/contenttypes/fields.py
index e55766aa6f..ed98ecb48c 100644
--- a/django/contrib/contenttypes/fields.py
+++ b/django/contrib/contenttypes/fields.py
@@ -545,6 +545,12 @@ def create_generic_related_manager(superclass, rel):
             db = self._db or router.db_for_read(self.model, instance=self.instance)
             return queryset.using(db).filter(**self.core_filters)
 
+        def _remove_prefetched_objects(self):
+            try:
+                self.instance._prefetched_objects_cache.pop(self.prefetch_cache_name)
+            except (AttributeError, KeyError):
+                pass  # nothing to clear from cache
+
         def get_queryset(self):
             try:
                 return self.instance._prefetched_objects_cache[self.prefetch_cache_name]
@@ -577,6 +583,7 @@ def create_generic_related_manager(superclass, rel):
             )
 
         def add(self, *objs, bulk=True):
+            self._remove_prefetched_objects()
             db = router.db_for_write(self.model, instance=self.instance)
 
             def check_and_update_obj(obj):
@@ -620,6 +627,7 @@ def create_generic_related_manager(superclass, rel):
         clear.alters_data = True
 
         def _clear(self, queryset, bulk):
+            self._remove_prefetched_objects()
             db = router.db_for_write(self.model, instance=self.instance)
             queryset = queryset.using(db)
             if bulk:
@@ -656,6 +664,7 @@ def create_generic_related_manager(superclass, rel):
         set.alters_data = True
 
         def create(self, **kwargs):
+            self._remove_prefetched_objects()
             kwargs[self.content_type_field_name] = self.content_type
             kwargs[self.object_id_field_name] = self.pk_val
             db = router.db_for_write(self.model, instance=self.instance)
diff --git a/tests/generic_relations/tests.py b/tests/generic_relations/tests.py
index 4c27b6f3d5..2e99c5b5cf 100644
--- a/tests/generic_relations/tests.py
+++ b/tests/generic_relations/tests.py
@@ -499,6 +499,53 @@ class GenericRelationsTests(TestCase):
         tag = TaggedItem(content_object=spinach)
         self.assertEqual(tag.content_object, spinach)
 
+    def test_create_after_prefetch(self):
+        platypus = Animal.objects.prefetch_related('tags').get(pk=self.platypus.pk)
+        self.assertSequenceEqual(platypus.tags.all(), [])
+        weird_tag = platypus.tags.create(tag='weird')
+        self.assertSequenceEqual(platypus.tags.all(), [weird_tag])
+
+    def test_add_after_prefetch(self):
+        platypus = Animal.objects.prefetch_related('tags').get(pk=self.platypus.pk)
+        self.assertSequenceEqual(platypus.tags.all(), [])
+        weird_tag = TaggedItem.objects.create(tag='weird', content_object=platypus)
+        platypus.tags.add(weird_tag)
+        self.assertSequenceEqual(platypus.tags.all(), [weird_tag])
+
+    def test_remove_after_prefetch(self):
+        weird_tag = self.platypus.tags.create(tag='weird')
+        platypus = Animal.objects.prefetch_related('tags').get(pk=self.platypus.pk)
+        self.assertSequenceEqual(platypus.tags.all(), [weird_tag])
+        platypus.tags.remove(weird_tag)
+        self.assertSequenceEqual(platypus.tags.all(), [])
+
+    def test_clear_after_prefetch(self):
+        weird_tag = self.platypus.tags.create(tag='weird')
+        platypus = Animal.objects.prefetch_related('tags').get(pk=self.platypus.pk)
+        self.assertSequenceEqual(platypus.tags.all(), [weird_tag])
+        platypus.tags.clear()
+        self.assertSequenceEqual(platypus.tags.all(), [])
+
+    def test_set_after_prefetch(self):
+        platypus = Animal.objects.prefetch_related('tags').get(pk=self.platypus.pk)
+        self.assertSequenceEqual(platypus.tags.all(), [])
+        furry_tag = TaggedItem.objects.create(tag='furry', content_object=platypus)
+        platypus.tags.set([furry_tag])
+        self.assertSequenceEqual(platypus.tags.all(), [furry_tag])
+        weird_tag = TaggedItem.objects.create(tag='weird', content_object=platypus)
+        platypus.tags.set([weird_tag])
+        self.assertSequenceEqual(platypus.tags.all(), [weird_tag])
+
+    def test_add_then_remove_after_prefetch(self):
+        furry_tag = self.platypus.tags.create(tag='furry')
+        platypus = Animal.objects.prefetch_related('tags').get(pk=self.platypus.pk)
+        self.assertSequenceEqual(platypus.tags.all(), [furry_tag])
+        weird_tag = self.platypus.tags.create(tag='weird')
+        platypus.tags.add(weird_tag)
+        self.assertSequenceEqual(platypus.tags.all(), [furry_tag, weird_tag])
+        platypus.tags.remove(weird_tag)
+        self.assertSequenceEqual(platypus.tags.all(), [furry_tag])
+
 
 class ProxyRelatedModelTest(TestCase):
     def test_default_behavior(self):