diff --git a/doc/source/whatsnew/v1.2.0.rst b/doc/source/whatsnew/v1.2.0.rst
index 09cb024cbd95c..b5fbd277a3228 100644
--- a/doc/source/whatsnew/v1.2.0.rst
+++ b/doc/source/whatsnew/v1.2.0.rst
@@ -352,7 +352,7 @@ Deprecations
 - :class:`Index` methods ``&``, ``|``, and ``^`` behaving as the set operations :meth:`Index.intersection`, :meth:`Index.union`, and :meth:`Index.symmetric_difference`, respectively, are deprecated and in the future will behave as pointwise boolean operations matching :class:`Series` behavior.  Use the named set methods instead (:issue:`36758`)
 - :meth:`Categorical.is_dtype_equal` and :meth:`CategoricalIndex.is_dtype_equal` are deprecated, will be removed in a future version (:issue:`37545`)
 - :meth:`Series.slice_shift` and :meth:`DataFrame.slice_shift` are deprecated, use :meth:`Series.shift` or :meth:`DataFrame.shift` instead (:issue:`37601`)
-
+- Partial slicing on unordered :class:`DatetimeIndexes` with keys, which are not in Index is deprecated and will be removed in a future version (:issue:`18531`)
 
 .. ---------------------------------------------------------------------------
 
diff --git a/pandas/core/indexes/datetimes.py b/pandas/core/indexes/datetimes.py
index 9744eb0ecbb88..a1a1a83555f95 100644
--- a/pandas/core/indexes/datetimes.py
+++ b/pandas/core/indexes/datetimes.py
@@ -803,14 +803,25 @@ def slice_indexer(self, start=None, end=None, step=None, kind=None):
                 end is None or isinstance(end, str)
             ):
                 mask = np.array(True)
+                deprecation_mask = np.array(True)
                 if start is not None:
                     start_casted = self._maybe_cast_slice_bound(start, "left", kind)
                     mask = start_casted <= self
+                    deprecation_mask = start_casted == self
 
                 if end is not None:
                     end_casted = self._maybe_cast_slice_bound(end, "right", kind)
                     mask = (self <= end_casted) & mask
-
+                    deprecation_mask = (end_casted == self) | deprecation_mask
+
+                if not deprecation_mask.any():
+                    warnings.warn(
+                        "Value based partial slicing on non-monotonic DatetimeIndexes "
+                        "with non-existing keys is deprecated and will raise a "
+                        "KeyError in a future Version.",
+                        FutureWarning,
+                        stacklevel=5,
+                    )
                 indexer = mask.nonzero()[0][::step]
                 if len(indexer) == len(self):
                     return slice(None)
diff --git a/pandas/tests/indexes/datetimes/test_partial_slicing.py b/pandas/tests/indexes/datetimes/test_partial_slicing.py
index 57dc46e1fb415..05ee67eee0da5 100644
--- a/pandas/tests/indexes/datetimes/test_partial_slicing.py
+++ b/pandas/tests/indexes/datetimes/test_partial_slicing.py
@@ -312,17 +312,22 @@ def test_partial_slicing_with_multiindex(self):
 
     def test_partial_slice_doesnt_require_monotonicity(self):
         # For historical reasons.
-        s = Series(np.arange(10), date_range("2014-01-01", periods=10))
+        ser = Series(np.arange(10), date_range("2014-01-01", periods=10))
 
-        nonmonotonic = s[[3, 5, 4]]
+        nonmonotonic = ser[[3, 5, 4]]
         expected = nonmonotonic.iloc[:0]
         timestamp = Timestamp("2014-01-10")
+        with tm.assert_produces_warning(FutureWarning):
+            result = nonmonotonic["2014-01-10":]
+        tm.assert_series_equal(result, expected)
 
-        tm.assert_series_equal(nonmonotonic["2014-01-10":], expected)
         with pytest.raises(KeyError, match=r"Timestamp\('2014-01-10 00:00:00'\)"):
             nonmonotonic[timestamp:]
 
-        tm.assert_series_equal(nonmonotonic.loc["2014-01-10":], expected)
+        with tm.assert_produces_warning(FutureWarning):
+            result = nonmonotonic.loc["2014-01-10":]
+        tm.assert_series_equal(result, expected)
+
         with pytest.raises(KeyError, match=r"Timestamp\('2014-01-10 00:00:00'\)"):
             nonmonotonic.loc[timestamp:]
 
diff --git a/pandas/tests/indexing/test_loc.py b/pandas/tests/indexing/test_loc.py
index 9aab867df4b17..b45eddc3ac49c 100644
--- a/pandas/tests/indexing/test_loc.py
+++ b/pandas/tests/indexing/test_loc.py
@@ -1564,6 +1564,15 @@ def test_loc_getitem_slice_label_td64obj(self, start, stop, expected_slice):
         expected = ser.iloc[expected_slice]
         tm.assert_series_equal(result, expected)
 
+    @pytest.mark.parametrize("start", ["2018", "2020"])
+    def test_loc_getitem_slice_unordered_dt_index(self, frame_or_series, start):
+        obj = frame_or_series(
+            [1, 2, 3],
+            index=[Timestamp("2016"), Timestamp("2019"), Timestamp("2017")],
+        )
+        with tm.assert_produces_warning(FutureWarning):
+            obj.loc[start:"2022"]
+
 
 class TestLocBooleanMask:
     def test_loc_setitem_bool_mask_timedeltaindex(self):
diff --git a/pandas/tests/series/indexing/test_datetime.py b/pandas/tests/series/indexing/test_datetime.py
index 44fb8dc519322..71ddf72562f36 100644
--- a/pandas/tests/series/indexing/test_datetime.py
+++ b/pandas/tests/series/indexing/test_datetime.py
@@ -526,7 +526,8 @@ def compare(slobj):
         tm.assert_series_equal(result, expected)
 
     compare(slice("2011-01-01", "2011-01-15"))
-    compare(slice("2010-12-30", "2011-01-15"))
+    with tm.assert_produces_warning(FutureWarning):
+        compare(slice("2010-12-30", "2011-01-15"))
     compare(slice("2011-01-01", "2011-01-16"))
 
     # partial ranges