diff --git a/Lib/pdb.py b/Lib/pdb.py
--- a/Lib/pdb.py
+++ b/Lib/pdb.py
@@ -1669,6 +1669,9 @@
             # In most cases SystemExit does not warrant a post-mortem session.
             print("The program exited via sys.exit(). Exit status:", end=' ')
             print(sys.exc_info()[1])
+        except SyntaxError:
+            traceback.print_exc()
+            sys.exit(1)
         except:
             traceback.print_exc()
             print("Uncaught exception. Entering post mortem debugging")
diff --git a/Lib/test/test_pdb.py b/Lib/test/test_pdb.py
--- a/Lib/test/test_pdb.py
+++ b/Lib/test/test_pdb.py
@@ -1043,6 +1043,22 @@
         self.assertNotIn('Error', stdout.decode(),
                          "Got an error running test script under PDB")
 
+    def test_issue16180(self):
+        # A syntax error in the debuggee.
+        script = """
+            def foo:
+                pass
+
+            foo()
+        """
+        commands = ''
+        expected = "SyntaxError: invalid syntax"
+        stdout, stderr = self.run_pdb(script, commands)
+        self.assertIn(expected, stdout,
+            '\n\nExpected:\n{}\nGot:\n{}\n'
+            'Fail to handle a syntax error in the debuggee.'
+            .format(expected, stdout))
+
     def tearDown(self):
         support.unlink(support.TESTFN)