diff --git a/Lib/test/test_typing.py b/Lib/test/test_typing.py
index 58781e52aca6d8..703fe84f3aad10 100644
--- a/Lib/test/test_typing.py
+++ b/Lib/test/test_typing.py
@@ -978,6 +978,38 @@ def foo(**kwargs: Unpack[Movie]): ...
         self.assertEqual(repr(foo.__annotations__['kwargs']),
                          f"typing.Unpack[{__name__}.Movie]")
 
+    def test_builtin_tuple(self):
+        Ts = TypeVarTuple("Ts")
+
+        class Old(Generic[*Ts]): ...
+        class New[*Ts]: ...
+
+        PartOld = Old[int, *Ts]
+        self.assertEqual(PartOld[str].__args__, (int, str))
+        self.assertEqual(PartOld[*tuple[str]].__args__, (int, str))
+        self.assertEqual(PartOld[*Tuple[str]].__args__, (int, str))
+        self.assertEqual(PartOld[Unpack[tuple[str]]].__args__, (int, str))
+        self.assertEqual(PartOld[Unpack[Tuple[str]]].__args__, (int, str))
+
+        PartNew = New[int, *Ts]
+        self.assertEqual(PartNew[str].__args__, (int, str))
+        self.assertEqual(PartNew[*tuple[str]].__args__, (int, str))
+        self.assertEqual(PartNew[*Tuple[str]].__args__, (int, str))
+        self.assertEqual(PartNew[Unpack[tuple[str]]].__args__, (int, str))
+        self.assertEqual(PartNew[Unpack[Tuple[str]]].__args__, (int, str))
+
+    def test_unpack_wrong_type(self):
+        Ts = TypeVarTuple("Ts")
+        class Gen[*Ts]: ...
+        PartGen = Gen[int, *Ts]
+
+        bad_unpack_param = re.escape("Unpack[...] must be used with a tuple type")
+        with self.assertRaisesRegex(TypeError, bad_unpack_param):
+            PartGen[Unpack[list[int]]]
+        with self.assertRaisesRegex(TypeError, bad_unpack_param):
+            PartGen[Unpack[List[int]]]
+
+
 class TypeVarTupleTests(BaseTestCase):
 
     def assertEndsWith(self, string, tail):
diff --git a/Lib/typing.py b/Lib/typing.py
index a0b68f593ca0d9..b3f4ba99f9ec21 100644
--- a/Lib/typing.py
+++ b/Lib/typing.py
@@ -1786,8 +1786,9 @@ def __typing_unpacked_tuple_args__(self):
         assert self.__origin__ is Unpack
         assert len(self.__args__) == 1
         arg, = self.__args__
-        if isinstance(arg, _GenericAlias):
-            assert arg.__origin__ is tuple
+        if isinstance(arg, (_GenericAlias, types.GenericAlias)):
+            if arg.__origin__ is not tuple:
+                raise TypeError("Unpack[...] must be used with a tuple type")
             return arg.__args__
         return None
 
diff --git a/Misc/NEWS.d/next/Library/2024-04-22-20-42-29.gh-issue-118168.Igni7h.rst b/Misc/NEWS.d/next/Library/2024-04-22-20-42-29.gh-issue-118168.Igni7h.rst
new file mode 100644
index 00000000000000..78c3e0fe17979a
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2024-04-22-20-42-29.gh-issue-118168.Igni7h.rst
@@ -0,0 +1,4 @@
+Fix incorrect argument substitution when :data:`typing.Unpack` is used with
+the builtin :class:`tuple`. :data:`!typing.Unpack` now raises
+:exc:`TypeError` when used with certain invalid types. Patch by Jelle
+Zijlstra.