diff --git a/django/test/testcases.py b/django/test/testcases.py
index 9b25a0b937..8d3265a5b9 100644
--- a/django/test/testcases.py
+++ b/django/test/testcases.py
@@ -518,6 +518,12 @@ class SimpleTestCase(unittest.TestCase):
         if msg_prefix:
             msg_prefix += ": "
 
+        if template_name is not None and response is not None and not hasattr(response, 'templates'):
+            raise ValueError(
+                "assertTemplateUsed() and assertTemplateNotUsed() are only "
+                "usable on responses fetched using the Django test Client."
+            )
+
         if not hasattr(response, 'templates') or (response is None and template_name):
             if response:
                 template_name = response
diff --git a/tests/test_utils/tests.py b/tests/test_utils/tests.py
index 99ddaf87ef..ddef92c193 100644
--- a/tests/test_utils/tests.py
+++ b/tests/test_utils/tests.py
@@ -385,6 +385,18 @@ class AssertTemplateUsedContextManagerTests(TestCase):
             with self.assertTemplateUsed('template_used/base.html'):
                 render_to_string('template_used/alternative.html')
 
+    def test_assert_used_on_http_response(self):
+        response = HttpResponse()
+        error_msg = (
+            'assertTemplateUsed() and assertTemplateNotUsed() are only '
+            'usable on responses fetched using the Django test Client.'
+        )
+        with self.assertRaisesMessage(ValueError, error_msg):
+            self.assertTemplateUsed(response, 'template.html')
+
+        with self.assertRaisesMessage(ValueError, error_msg):
+            self.assertTemplateNotUsed(response, 'template.html')
+
 
 class HTMLEqualTests(TestCase):
     def test_html_parser(self):