diff --git a/doc/source/whatsnew/v1.4.0.rst b/doc/source/whatsnew/v1.4.0.rst
index a593a03de5c25..02e2523d265e4 100644
--- a/doc/source/whatsnew/v1.4.0.rst
+++ b/doc/source/whatsnew/v1.4.0.rst
@@ -605,7 +605,7 @@ Indexing
 - Bug in :meth:`Series.__setitem__` with an integer dtype other than ``int64`` setting with a ``range`` object unnecessarily upcasting to ``int64`` (:issue:`44261`)
 - Bug in :meth:`Series.__setitem__` with a boolean mask indexer setting a listlike value of length 1 incorrectly broadcasting that value (:issue:`44265`)
 - Bug in :meth:`DataFrame.loc.__setitem__` and :meth:`DataFrame.iloc.__setitem__` with mixed dtypes sometimes failing to operate in-place (:issue:`44345`)
--
+- Bug in :meth:`DataFrame.loc.__getitem__` incorrectly raising ``KeyError`` when selecting a single column with a boolean key (:issue:`44322`).
 
 Missing
 ^^^^^^^
diff --git a/pandas/core/indexing.py b/pandas/core/indexing.py
index 91f1415178471..7d12a27aed84a 100644
--- a/pandas/core/indexing.py
+++ b/pandas/core/indexing.py
@@ -994,7 +994,7 @@ def _validate_key(self, key, axis: int):
         # slice of labels (where start-end in labels)
         # slice of integers (only if in the labels)
         # boolean not in slice and with boolean index
-        if isinstance(key, bool) and not is_bool_dtype(self.obj.index):
+        if isinstance(key, bool) and not is_bool_dtype(self.obj._get_axis(axis)):
             raise KeyError(
                 f"{key}: boolean label can not be used without a boolean index"
             )
diff --git a/pandas/tests/indexing/test_loc.py b/pandas/tests/indexing/test_loc.py
index 63d1568ed4d43..a07928b40ad0e 100644
--- a/pandas/tests/indexing/test_loc.py
+++ b/pandas/tests/indexing/test_loc.py
@@ -178,6 +178,26 @@ def test_column_types_consistent(self):
         )
         tm.assert_frame_equal(df, expected)
 
+    @pytest.mark.parametrize(
+        "obj, key, exp",
+        [
+            (
+                DataFrame([[1]], columns=Index([False])),
+                IndexSlice[:, False],
+                Series([1], name=False),
+            ),
+            (Series([1], index=Index([False])), False, [1]),
+            (DataFrame([[1]], index=Index([False])), False, Series([1], name=False)),
+        ],
+    )
+    def test_loc_getitem_single_boolean_arg(self, obj, key, exp):
+        # GH 44322
+        res = obj.loc[key]
+        if isinstance(exp, (DataFrame, Series)):
+            tm.assert_equal(res, exp)
+        else:
+            assert res == exp
+
 
 class TestLoc2:
     # TODO: better name, just separating out things that rely on base class