diff --git a/doc/source/whatsnew/v0.24.0.txt b/doc/source/whatsnew/v0.24.0.txt
index 6ace245a4bae1..0e1eb1a4e842b 100644
--- a/doc/source/whatsnew/v0.24.0.txt
+++ b/doc/source/whatsnew/v0.24.0.txt
@@ -1118,6 +1118,7 @@ Datetimelike
 - Bug in :func:`DataFrame.combine` with datetimelike values raising a TypeError (:issue:`23079`)
 - Bug in :func:`date_range` with frequency of ``Day`` or higher where dates sufficiently far in the future could wrap around to the past instead of raising ``OutOfBoundsDatetime`` (:issue:`14187`)
 - Bug in :class:`PeriodIndex` with attribute ``freq.n`` greater than 1 where adding a :class:`DateOffset` object would return incorrect results (:issue:`23215`)
+- Bug in :class:`Series` that interpreted string indices as lists of characters when setting datetimelike values (:issue:`23451`)
 
 Timedelta
 ^^^^^^^^^
diff --git a/pandas/core/series.py b/pandas/core/series.py
index cb8371ba086ba..6971b0b0c78e0 100644
--- a/pandas/core/series.py
+++ b/pandas/core/series.py
@@ -947,7 +947,9 @@ def _set_with(self, key, value):
                 except Exception:
                     pass
 
-            if not isinstance(key, (list, Series, np.ndarray, Series)):
+            if is_scalar(key):
+                key = [key]
+            elif not isinstance(key, (list, Series, np.ndarray)):
                 try:
                     key = list(key)
                 except Exception:
diff --git a/pandas/tests/series/test_datetime_values.py b/pandas/tests/series/test_datetime_values.py
index 2f6efc112819c..f3ae2b1e6ad15 100644
--- a/pandas/tests/series/test_datetime_values.py
+++ b/pandas/tests/series/test_datetime_values.py
@@ -548,3 +548,10 @@ def test_minmax_nat_series(self, nat):
     def test_minmax_nat_dataframe(self, nat):
         assert nat.min()[0] is pd.NaT
         assert nat.max()[0] is pd.NaT
+
+    def test_setitem_with_string_index(self):
+        # GH 23451
+        x = pd.Series([1, 2, 3], index=['Date', 'b', 'other'])
+        x['Date'] = date.today()
+        assert x.Date == date.today()
+        assert x['Date'] == date.today()