diff --git a/botocore/awsrequest.py b/botocore/awsrequest.py
index 9123e65c9d..84a1959bd2 100644
--- a/botocore/awsrequest.py
+++ b/botocore/awsrequest.py
@@ -92,7 +92,7 @@ def request(self, method, url, body=None, headers=None, *args, **kwargs):
             self._expect_header_set = True
         else:
             self._expect_header_set = False
-            self.response_class = self._original_response_cls
+        self.response_class = self._original_response_cls
         rval = super().request(method, url, body, headers, *args, **kwargs)
         self._expect_header_set = False
         return rval
diff --git a/tests/unit/test_awsrequest.py b/tests/unit/test_awsrequest.py
index a29a846116..be2e76aa79 100644
--- a/tests/unit/test_awsrequest.py
+++ b/tests/unit/test_awsrequest.py
@@ -486,6 +486,46 @@ def test_expect_100_continue_no_response_from_server(self):
             response = conn.getresponse()
             self.assertEqual(response.status, 307)
 
+    def test_expect_100_continue_followed_by_another_request(self):
+        with mock.patch('urllib3.util.wait_for_read') as wait_mock:
+            # Shows the server first sending a 200 ok response
+            # then a 200 ok response.
+            s = FakeSocket(
+                b'HTTP/1.1 200 OK\r\n'
+                b'Content-Length: 0\r\n'
+                b'\r\n'
+                b'HTTP/1.1 100 Continue\r\n'
+                b'\r\n'
+                b'HTTP/1.1 200 OK\r\n'
+                b'Content-Length: 0\r\n'
+            )
+            conn = AWSHTTPConnection('s3.amazonaws.com', 443)
+            conn.sock = s
+            wait_mock.return_value = True
+
+            # The first request expecting a 100 continue response.
+            # But the server will send a 200 ok instead.
+            conn.request(
+                'PUT', '/bucket/foo', b'body', {'Expect': b'100-continue'}
+            )
+            # Assert that we waited for the 100-continue response
+            self.assertEqual(wait_mock.call_count, 1)
+            response = conn.getresponse()
+            self.assertEqual(response.status, 200)
+            response.close()
+
+            # The client send the second request, expecting 100 continue either,
+            # using the same connection
+            conn.request(
+                'PUT', '/bucket/foo', b'body', {'Expect': b'100-continue'}
+            )
+            self.assertEqual(wait_mock.call_count, 2)
+            response = conn.getresponse()
+
+            # The second 'HTTP/1.1 200 OK\r\n' should be consumed by http.client.HTTPResponse._read_status().
+            # Only after this, the following header will be parsed correctly by email.parser.Parser.parsestr().
+            assert not getattr(response.headers, "defects", [])
+
     def test_message_body_is_file_like_object(self):
         # Shows the server first sending a 100 continue response
         # then a 200 ok response.