diff --git a/doc/source/whatsnew/v1.3.1.rst b/doc/source/whatsnew/v1.3.1.rst
index 65719a11243f8..82b4d2def0b5c 100644
--- a/doc/source/whatsnew/v1.3.1.rst
+++ b/doc/source/whatsnew/v1.3.1.rst
@@ -25,7 +25,7 @@ Fixed regressions
 
 Bug fixes
 ~~~~~~~~~
--
+-Bug in :meth:`pandas.DataFrame.astype` (:issue:`42396`)
 -
 
 .. ---------------------------------------------------------------------------
diff --git a/pandas/core/dtypes/cast.py b/pandas/core/dtypes/cast.py
index 15a18d5027274..651df62623fd2 100644
--- a/pandas/core/dtypes/cast.py
+++ b/pandas/core/dtypes/cast.py
@@ -1099,6 +1099,9 @@ def astype_nansafe(
         flat = arr.ravel("K")
         result = astype_nansafe(flat, dtype, copy=copy, skipna=skipna)
         order: Literal["C", "F"] = "F" if flags.f_contiguous else "C"
+        order: Literal["C", "F"] = (
+            "F" if (not flags.f_contiguous and not flags.c_contiguous) else order
+        )
         # error: Item "ExtensionArray" of "Union[ExtensionArray, ndarray]" has no
         # attribute "reshape"
         return result.reshape(arr.shape, order=order)  # type: ignore[union-attr]
diff --git a/pandas/tests/dtypes/test_dtypes.py b/pandas/tests/dtypes/test_dtypes.py
index abb29ce66fd34..ae3f85a7f1272 100644
--- a/pandas/tests/dtypes/test_dtypes.py
+++ b/pandas/tests/dtypes/test_dtypes.py
@@ -1095,3 +1095,16 @@ def test_period_dtype_compare_to_string():
     dtype = PeriodDtype(freq="M")
     assert (dtype == "period[M]") is True
     assert (dtype != "period[M]") is False
+
+
+@pytest.mark.parametrize(
+    "dtype", ["int_", "int8", "int16", "int32", "uint16", "uint32", "uint64"]
+)
+def test_dtype_frame_order_astype(dtype):
+
+    # GH 42396
+    npa = np.random.RandomState(0).randint(100, size=(20, 8))
+    df = pd.DataFrame(npa, columns=[f"c{i}" for i in range(8)])
+    expected = df.iloc[:6, :3]
+    result = df.iloc[:6, :3].astype(dtype)
+    tm.assert_almost_equal(expected, result, check_dtype=False)