diff --git a/doc/source/whatsnew/v1.5.3.rst b/doc/source/whatsnew/v1.5.3.rst
index cb99495b837b2..a0c38f1f81538 100644
--- a/doc/source/whatsnew/v1.5.3.rst
+++ b/doc/source/whatsnew/v1.5.3.rst
@@ -28,6 +28,7 @@ Bug fixes
 ~~~~~~~~~
 - Bug in :meth:`.Styler.to_excel` leading to error when unrecognized ``border-style`` (e.g. ``"hair"``) provided to Excel writers (:issue:`48649`)
 - Bug when chaining several :meth:`.Styler.concat` calls, only the last styler was concatenated (:issue:`49207`)
+- Fixed bug when instantiating a :class:`DataFrame` subclass inheriting from ``typing.Generic`` that triggered a ``UserWarning`` on python 3.11 (:issue:`49649`)
 -
 
 .. ---------------------------------------------------------------------------
diff --git a/pandas/_libs/lib.pyx b/pandas/_libs/lib.pyx
index 439136d17fed2..d2c2697c05812 100644
--- a/pandas/_libs/lib.pyx
+++ b/pandas/_libs/lib.pyx
@@ -1,7 +1,10 @@
 from collections import abc
 from decimal import Decimal
 from enum import Enum
-from typing import Literal
+from typing import (
+    Literal,
+    _GenericAlias,
+)
 import warnings
 
 cimport cython
@@ -1136,7 +1139,8 @@ cdef inline bint c_is_list_like(object obj, bint allow_sets) except -1:
         # equiv: `isinstance(obj, abc.Iterable)`
         getattr(obj, "__iter__", None) is not None and not isinstance(obj, type)
         # we do not count strings/unicode/bytes as list-like
-        and not isinstance(obj, (str, bytes))
+        # exclude Generic types that have __iter__
+        and not isinstance(obj, (str, bytes, _GenericAlias))
         # exclude zero-dimensional duck-arrays, effectively scalars
         and not (hasattr(obj, "ndim") and obj.ndim == 0)
         # exclude sets if allow_sets is False
diff --git a/pandas/tests/dtypes/test_inference.py b/pandas/tests/dtypes/test_inference.py
index f08d6b8c9feb8..948d14c1bd1f9 100644
--- a/pandas/tests/dtypes/test_inference.py
+++ b/pandas/tests/dtypes/test_inference.py
@@ -18,6 +18,10 @@
 from numbers import Number
 import re
 import sys
+from typing import (
+    Generic,
+    TypeVar,
+)
 
 import numpy as np
 import pytest
@@ -228,6 +232,22 @@ def __getitem__(self, item):
     assert not inference.is_list_like(NotListLike())
 
 
+def test_is_list_like_generic():
+    # GH 49649
+    # is_list_like was yielding false positives for Generic classes in python 3.11
+    T = TypeVar("T")
+
+    class MyDataFrame(DataFrame, Generic[T]):
+        ...
+
+    tstc = MyDataFrame[int]
+    tst = MyDataFrame[int]({"x": [1, 2, 3]})
+
+    assert not inference.is_list_like(tstc)
+    assert isinstance(tst, DataFrame)
+    assert inference.is_list_like(tst)
+
+
 def test_is_sequence():
     is_seq = inference.is_sequence
     assert is_seq((1, 2))