diff --git a/doc/source/whatsnew/v1.3.0.rst b/doc/source/whatsnew/v1.3.0.rst
index 414794dd6a56e..37f560807f1ca 100644
--- a/doc/source/whatsnew/v1.3.0.rst
+++ b/doc/source/whatsnew/v1.3.0.rst
@@ -948,6 +948,8 @@ Numeric
 - Bug in :meth:`Series.count` would result in an ``int32`` result on 32-bit platforms when argument ``level=None`` (:issue:`40908`)
 - Bug in :class:`Series` and :class:`DataFrame` reductions with methods ``any`` and ``all`` not returning Boolean results for object data (:issue:`12863`, :issue:`35450`, :issue:`27709`)
 - Bug in :meth:`Series.clip` would fail if the Series contains NA values and has nullable int or float as a data type (:issue:`40851`)
+- Bug in :meth:`UInt64Index.where` and :meth:`UInt64Index.putmask` with an ``np.int64`` dtype ``other`` incorrectly raising ``TypeError`` (:issue:`41974`)
+
 
 Conversion
 ^^^^^^^^^^
diff --git a/pandas/core/indexes/numeric.py b/pandas/core/indexes/numeric.py
index ea2d5d9eec6ac..ce93cdff09ae0 100644
--- a/pandas/core/indexes/numeric.py
+++ b/pandas/core/indexes/numeric.py
@@ -370,6 +370,16 @@ class UInt64Index(IntegerIndex):
     _default_dtype = np.dtype(np.uint64)
     _dtype_validation_metadata = (is_unsigned_integer_dtype, "unsigned integer")
 
+    def _validate_fill_value(self, value):
+        # e.g. np.array([1]) we want np.array([1], dtype=np.uint64)
+        #  see test_where_uin64
+        super()._validate_fill_value(value)
+        if hasattr(value, "dtype") and is_signed_integer_dtype(value.dtype):
+            if (value >= 0).all():
+                return value.astype(self.dtype)
+            raise TypeError
+        return value
+
 
 class Float64Index(NumericIndex):
     _index_descr_args = {
diff --git a/pandas/tests/indexes/numeric/test_indexing.py b/pandas/tests/indexes/numeric/test_indexing.py
index 5f2f8f75045bb..540dbde609470 100644
--- a/pandas/tests/indexes/numeric/test_indexing.py
+++ b/pandas/tests/indexes/numeric/test_indexing.py
@@ -376,6 +376,19 @@ def test_where(self, klass, index):
         result = index.where(klass(cond))
         tm.assert_index_equal(result, expected)
 
+    def test_where_uin64(self):
+        idx = UInt64Index([0, 6, 2])
+        mask = np.array([False, True, False])
+        other = np.array([1], dtype=np.int64)
+
+        expected = UInt64Index([1, 6, 1])
+
+        result = idx.where(mask, other)
+        tm.assert_index_equal(result, expected)
+
+        result = idx.putmask(~mask, other)
+        tm.assert_index_equal(result, expected)
+
 
 class TestTake:
     @pytest.mark.parametrize("klass", [Float64Index, Int64Index, UInt64Index])