diff --git a/Lib/test/test_typing.py b/Lib/test/test_typing.py
index 5c1e907070ee41..2c0958eab1f5fa 100644
--- a/Lib/test/test_typing.py
+++ b/Lib/test/test_typing.py
@@ -4947,9 +4947,10 @@ def _source(self):
     def test_multiple_inheritance(self):
         class A:
             pass
-        with self.assertRaises(TypeError):
-            class X(NamedTuple, A):
-                x: int
+        class X(NamedTuple, A):
+            x: int
+        class Y(X, A):
+            y: int
 
     def test_namedtuple_keyword_usage(self):
         LocalEmployee = NamedTuple("LocalEmployee", name=str, age=int)
@@ -5282,6 +5283,11 @@ def test_get_type_hints(self):
             {'a': typing.Optional[int], 'b': int}
         )
 
+    def test_generic_subclasses(self):
+        T = TypeVar("T")
+        class GenericNamedTuple(NamedTuple, Generic[T]):
+            pass
+
 
 class IOTests(BaseTestCase):
 
diff --git a/Lib/typing.py b/Lib/typing.py
index abb8bcefc5c04a..42f14e311f6783 100644
--- a/Lib/typing.py
+++ b/Lib/typing.py
@@ -2601,7 +2601,9 @@ def _make_nmtuple(name, types, module, defaults = ()):
              for n, t in types}
     nm_tpl = collections.namedtuple(name, fields,
                                     defaults=defaults, module=module)
-    nm_tpl.__annotations__ = nm_tpl.__new__.__annotations__ = types
+    nm_tpl.__annotations__ = types
+    nm_tpl.__new__.__annotations__ = types
+    nm_tpl.__new__.__defaults__ = tuple(defaults)
     return nm_tpl
 
 
@@ -2616,7 +2618,9 @@ def _make_nmtuple(name, types, module, defaults = ()):
 class NamedTupleMeta(type):
 
     def __new__(cls, typename, bases, ns):
-        assert bases[0] is _NamedTuple
+        if ns.get('_root', False):
+            return super().__new__(cls, typename, bases, ns)
+        assert NamedTuple in bases
         types = ns.get('__annotations__', {})
         default_names = []
         for field_name in types:
@@ -2639,7 +2643,7 @@ def __new__(cls, typename, bases, ns):
         return nm_tpl
 
 
-def NamedTuple(typename, fields=None, /, **kwargs):
+class NamedTuple(metaclass=NamedTupleMeta):
     """Typed version of namedtuple.
 
     Usage in Python versions >= 3.6::
@@ -2663,22 +2667,15 @@ class Employee(NamedTuple):
 
         Employee = NamedTuple('Employee', [('name', str), ('id', int)])
     """
-    if fields is None:
-        fields = kwargs.items()
-    elif kwargs:
-        raise TypeError("Either list of fields or keywords"
-                        " can be provided to NamedTuple, not both")
-    return _make_nmtuple(typename, fields, module=_caller())
-
-_NamedTuple = type.__new__(NamedTupleMeta, 'NamedTuple', (), {})
-
-def _namedtuple_mro_entries(bases):
-    if len(bases) > 1:
-        raise TypeError("Multiple inheritance with NamedTuple is not supported")
-    assert bases[0] is NamedTuple
-    return (_NamedTuple,)
-
-NamedTuple.__mro_entries__ = _namedtuple_mro_entries
+    _root = True
+
+    def __new__(cls, typename, fields=None, /, **kwargs):
+        if fields is None:
+            fields = kwargs.items()
+        elif kwargs:
+            raise TypeError("Either list of fields or keywords"
+                            " can be provided to NamedTuple, not both")
+        return _make_nmtuple(typename, fields, module=_caller())
 
 
 class _TypedDictMeta(type):
diff --git a/Misc/NEWS.d/next/Library/2022-03-08-20-13-08.bpo-43923.gefhqh.rst b/Misc/NEWS.d/next/Library/2022-03-08-20-13-08.bpo-43923.gefhqh.rst
new file mode 100644
index 00000000000000..d849cf05eaaa7f
--- /dev/null
+++ b/Misc/NEWS.d/next/Library/2022-03-08-20-13-08.bpo-43923.gefhqh.rst
@@ -0,0 +1,2 @@
+Multiple inheritance with :class:`typing.NamedTuple` now no longer raises an
+error.