diff --git a/doc/source/whatsnew/v1.6.0.rst b/doc/source/whatsnew/v1.6.0.rst
index a7c9a7eb88221..75e107bfb5892 100644
--- a/doc/source/whatsnew/v1.6.0.rst
+++ b/doc/source/whatsnew/v1.6.0.rst
@@ -109,6 +109,7 @@ Performance improvements
 - Performance improvement in :meth:`.GroupBy.mean` and :meth:`.GroupBy.var` for extension array dtypes (:issue:`37493`)
 - Performance improvement for :meth:`Series.value_counts` with nullable dtype (:issue:`48338`)
 - Performance improvement for :class:`Series` constructor passing integer numpy array with nullable dtype (:issue:`48338`)
+- Performance improvement in :meth:`DataFrame.loc` and :meth:`Series.loc` for tuple-based indexing of a :class:`MultiIndex` (:issue:`48384`)
 - Performance improvement for :meth:`MultiIndex.unique` (:issue:`48335`)
 - Performance improvement in ``var`` for nullable dtypes (:issue:`48379`).
 - Performance improvement to :func:`read_sas` with ``blank_missing=True`` (:issue:`48502`)
diff --git a/pandas/core/indexes/multi.py b/pandas/core/indexes/multi.py
index 9506e775ceb03..dd63ea94d5211 100644
--- a/pandas/core/indexes/multi.py
+++ b/pandas/core/indexes/multi.py
@@ -3466,22 +3466,35 @@ def _reorder_indexer(
         -------
         indexer : a sorted position indexer of self ordered as seq
         """
-        # If the index is lexsorted and the list_like label in seq are sorted
-        # then we do not need to sort
-        if self._is_lexsorted():
-            need_sort = False
-            for i, k in enumerate(seq):
-                if is_list_like(k):
-                    if not need_sort:
-                        k_codes = self.levels[i].get_indexer(k)
-                        k_codes = k_codes[k_codes >= 0]  # Filter absent keys
-                        # True if the given codes are not ordered
-                        need_sort = (k_codes[:-1] > k_codes[1:]).any()
-                elif isinstance(k, slice) and k.step is not None and k.step < 0:
+
+        # check if sorting is necessary
+        need_sort = False
+        for i, k in enumerate(seq):
+            if com.is_null_slice(k) or com.is_bool_indexer(k) or is_scalar(k):
+                pass
+            elif is_list_like(k):
+                if len(k) <= 1:  # type: ignore[arg-type]
+                    pass
+                elif self._is_lexsorted():
+                    # If the index is lexsorted and the list_like label
+                    # in seq are sorted then we do not need to sort
+                    k_codes = self.levels[i].get_indexer(k)
+                    k_codes = k_codes[k_codes >= 0]  # Filter absent keys
+                    # True if the given codes are not ordered
+                    need_sort = (k_codes[:-1] > k_codes[1:]).any()
+                else:
                     need_sort = True
-            # Bail out if both index and seq are sorted
-            if not need_sort:
-                return indexer
+            elif isinstance(k, slice):
+                if self._is_lexsorted():
+                    need_sort = k.step is not None and k.step < 0
+                else:
+                    need_sort = True
+            else:
+                need_sort = True
+            if need_sort:
+                break
+        if not need_sort:
+            return indexer
 
         n = len(self)
         keys: tuple[np.ndarray, ...] = ()
diff --git a/pandas/tests/indexes/multi/test_indexing.py b/pandas/tests/indexes/multi/test_indexing.py
index 9626352ac7e36..591b7abf60cc0 100644
--- a/pandas/tests/indexes/multi/test_indexing.py
+++ b/pandas/tests/indexes/multi/test_indexing.py
@@ -898,3 +898,29 @@ def test_pyint_engine():
     missing = tuple([0, 1] * 5 * N)
     result = index.get_indexer([missing] + [keys[i] for i in idces])
     tm.assert_numpy_array_equal(result, expected)
+
+
+@pytest.mark.parametrize(
+    "keys,expected",
+    [
+        ((slice(None), [5, 4]), [1, 0]),
+        ((slice(None), [4, 5]), [0, 1]),
+        (([True, False, True], [4, 6]), [0, 2]),
+        (([True, False, True], [6, 4]), [0, 2]),
+        ((2, [4, 5]), [0, 1]),
+        ((2, [5, 4]), [1, 0]),
+        (([2], [4, 5]), [0, 1]),
+        (([2], [5, 4]), [1, 0]),
+    ],
+)
+def test_get_locs_reordering(keys, expected):
+    # GH48384
+    idx = MultiIndex.from_arrays(
+        [
+            [2, 2, 1],
+            [4, 5, 6],
+        ]
+    )
+    result = idx.get_locs(keys)
+    expected = np.array(expected, dtype=np.intp)
+    tm.assert_numpy_array_equal(result, expected)