diff --git a/doc/source/whatsnew/v1.4.1.rst b/doc/source/whatsnew/v1.4.1.rst
index 1bd8da2d2b03c..21aab5058d25b 100644
--- a/doc/source/whatsnew/v1.4.1.rst
+++ b/doc/source/whatsnew/v1.4.1.rst
@@ -15,6 +15,7 @@ including other versions of pandas.
 Fixed regressions
 ~~~~~~~~~~~~~~~~~
 - Regression in :meth:`Series.mask` with ``inplace=True`` and ``PeriodDtype`` and an incompatible ``other`` coercing to a common dtype instead of raising (:issue:`45546`)
+- Regression in :meth:`Series.fillna` with ``downcast=False`` incorrectly downcasting ``object`` dtype (:issue:`45603`)
 - Regression in :meth:`DataFrame.loc.__setitem__` losing :class:`Index` name if :class:`DataFrame` was empty before (:issue:`45621`)
 -
 
diff --git a/pandas/core/internals/blocks.py b/pandas/core/internals/blocks.py
index 1bc27c80ef58e..5810f3515c4ae 100644
--- a/pandas/core/internals/blocks.py
+++ b/pandas/core/internals/blocks.py
@@ -528,6 +528,8 @@ def split_and_operate(self, func, *args, **kwargs) -> list[Block]:
 
     @final
     def _maybe_downcast(self, blocks: list[Block], downcast=None) -> list[Block]:
+        if downcast is False:
+            return blocks
 
         if self.dtype == _dtype_obj:
             # GH#44241 We downcast regardless of the argument;
@@ -541,10 +543,6 @@ def _maybe_downcast(self, blocks: list[Block], downcast=None) -> list[Block]:
 
         if downcast is None:
             return blocks
-        if downcast is False:
-            # turn if off completely
-            # TODO: not reached, deprecate in favor of downcast=None
-            return blocks
 
         return extend_blocks([b._downcast_2d(downcast) for b in blocks])
 
diff --git a/pandas/tests/frame/methods/test_fillna.py b/pandas/tests/frame/methods/test_fillna.py
index b5bdf6a70199c..21a45d9ee1f20 100644
--- a/pandas/tests/frame/methods/test_fillna.py
+++ b/pandas/tests/frame/methods/test_fillna.py
@@ -244,6 +244,12 @@ def test_fillna_downcast(self):
         expected = DataFrame({"a": [1, 0]})
         tm.assert_frame_equal(result, expected)
 
+    def test_fillna_downcast_false(self, frame_or_series):
+        # GH#45603 preserve object dtype with downcast=False
+        obj = frame_or_series([1, 2, 3], dtype="object")
+        result = obj.fillna("", downcast=False)
+        tm.assert_equal(result, obj)
+
     @pytest.mark.parametrize("columns", [["A", "A", "B"], ["A", "A"]])
     def test_fillna_dictlike_value_duplicate_colnames(self, columns):
         # GH#43476