diff --git a/packages/zarr-indexing/changes/4333.bugfix.md b/packages/zarr-indexing/changes/4333.bugfix.md
new file mode 100644
index 0000000000..0347c2d95d
--- /dev/null
+++ b/packages/zarr-indexing/changes/4333.bugfix.md
@@ -0,0 +1,4 @@
+Direct `IndexTransform.oindex` and `IndexTransform.vindex` selections now reject
+integer array coordinates outside the `np.intp` range before conversion.
+Previously, oversized `uint64` values could wrap to negative coordinates and
+silently select a different location in a domain containing negative coordinates.
diff --git a/packages/zarr-indexing/src/zarr_indexing/transform.py b/packages/zarr-indexing/src/zarr_indexing/transform.py
index cb29776476..975494490c 100644
--- a/packages/zarr-indexing/src/zarr_indexing/transform.py
+++ b/packages/zarr-indexing/src/zarr_indexing/transform.py
@@ -1541,7 +1541,7 @@ def _normalize_oindex_selection(
             (indices,) = np.nonzero(sel)
             result.append(indices.astype(np.intp))
         elif isinstance(sel, np.ndarray):
-            result.append(sel.astype(np.intp))
+            result.append(checked_affine(0, 1, sel))
         elif isinstance(sel, slice):
             result.append(sel)
         elif (scalar := as_scalar_index(sel)) is not None:
@@ -1553,7 +1553,9 @@ def _normalize_oindex_selection(
                 (indices,) = np.nonzero(array)
                 result.append(indices.astype(np.intp))
             else:
-                result.append(np.asarray(sel, dtype=np.intp))
+                # Advanced selection validation has already checked the element types.
+                integer_array = cast("npt.NDArray[np.integer[Any]]", array)
+                result.append(checked_affine(0, 1, integer_array))
         else:
             result.append(sel)
 
@@ -1743,9 +1745,11 @@ def _apply_vindex(transform: IndexTransform, selection: Any) -> IndexTransform:
             indices_tuple = np.nonzero(boolean_array)
             processed.extend(indices.astype(np.intp) for indices in indices_tuple)
         elif isinstance(sel, np.ndarray):
-            processed.append(sel.astype(np.intp))
+            processed.append(checked_affine(0, 1, sel))
         elif isinstance(sel, (list, tuple)):
-            processed.append(np.asarray(sel, dtype=np.intp))
+            # Advanced selection validation has already checked the element types.
+            integer_array = cast("npt.NDArray[np.integer[Any]]", np.asarray(sel))
+            processed.append(checked_affine(0, 1, integer_array))
         elif (scalar := as_scalar_index(sel)) is not None:
             processed.append(np.array([scalar], dtype=np.intp))
         else:
diff --git a/packages/zarr-indexing/tests/test_transform.py b/packages/zarr-indexing/tests/test_transform.py
index a13eaf6e28..9e8b24bf4a 100644
--- a/packages/zarr-indexing/tests/test_transform.py
+++ b/packages/zarr-indexing/tests/test_transform.py
@@ -763,6 +763,32 @@ def test_vindex_multiple_arrays_preserves_shared_axes(self) -> None:
         assert result.output[1].index_array.shape == (2,)
 
 
+@pytest.mark.parametrize("mode", ["oindex", "vindex"])
+@pytest.mark.parametrize("as_list", [False, True])
+@pytest.mark.parametrize("value", [2**63, 2**64 - 1])
+def test_direct_advanced_index_rejects_unsigned_overflow(
+    mode: str, as_list: bool, value: int
+) -> None:
+    """Narrowing must not turn huge positive coordinates into valid negative ones."""
+    transform = IndexTransform.identity(
+        IndexDomain(inclusive_min=(np.iinfo(np.intp).min,), exclusive_max=(0,))
+    )
+    selector = [value] if as_list else np.array([value], dtype=np.uint64)
+    with pytest.raises(OverflowError, match="outside np.intp range"):
+        getattr(transform, mode)[selector]
+
+
+@pytest.mark.parametrize("mode", ["oindex", "vindex"])
+@pytest.mark.parametrize("dtype", ["intp", "uint8", "uint64"])
+def test_direct_advanced_index_preserves_valid_coordinates(mode: str, dtype: str) -> None:
+    transform = IndexTransform.from_shape((5,))
+    selector = np.array([3, 0, 3], dtype=dtype)
+    selector.flags.writeable = False
+    result = getattr(transform, mode)[selector]
+    np.testing.assert_array_equal(result.apply_many(np.arange(3).reshape(3, 1)), [[3], [0], [3]])
+    np.testing.assert_array_equal(selector, [3, 0, 3])
+
+
 @pytest.mark.parametrize("mode", ["oindex", "vindex"])
 def test_direct_advanced_index_rejects_float_arrays(mode: str) -> None:
     helper = getattr(IndexTransform.from_shape((5,)), mode)