diff --git a/doc/whats-new.rst b/doc/whats-new.rst
index c1bfaba8756..cdc53685895 100644
--- a/doc/whats-new.rst
+++ b/doc/whats-new.rst
@@ -38,6 +38,8 @@ New Features
 Breaking changes
 ~~~~~~~~~~~~~~~~
 
+- Don't allow overwriting index variables with ``to_zarr`` region writes. (:issue:`8589`, :pull:`8876`).
+  By `Deepak Cherian <https://github.com/dcherian>`_.
 
 Deprecations
 ~~~~~~~~~~~~
diff --git a/xarray/backends/api.py b/xarray/backends/api.py
index d3026a535e2..24fc8b116d3 100644
--- a/xarray/backends/api.py
+++ b/xarray/backends/api.py
@@ -1562,9 +1562,7 @@ def _auto_detect_regions(ds, region, open_kwargs):
     return region
 
 
-def _validate_and_autodetect_region(
-    ds, region, mode, open_kwargs
-) -> tuple[dict[str, slice], bool]:
+def _validate_and_autodetect_region(ds, region, mode, open_kwargs) -> dict[str, slice]:
     if region == "auto":
         region = {dim: "auto" for dim in ds.dims}
 
@@ -1572,14 +1570,11 @@ def _validate_and_autodetect_region(
         raise TypeError(f"``region`` must be a dict, got {type(region)}")
 
     if any(v == "auto" for v in region.values()):
-        region_was_autodetected = True
         if mode != "r+":
             raise ValueError(
                 f"``mode`` must be 'r+' when using ``region='auto'``, got {mode}"
             )
         region = _auto_detect_regions(ds, region, open_kwargs)
-    else:
-        region_was_autodetected = False
 
     for k, v in region.items():
         if k not in ds.dims:
@@ -1612,7 +1607,7 @@ def _validate_and_autodetect_region(
             f".drop_vars({non_matching_vars!r})"
         )
 
-    return region, region_was_autodetected
+    return region
 
 
 def _validate_datatypes_for_zarr_append(zstore, dataset):
@@ -1784,12 +1779,9 @@ def to_zarr(
             storage_options=storage_options,
             zarr_version=zarr_version,
         )
-        region, region_was_autodetected = _validate_and_autodetect_region(
-            dataset, region, mode, open_kwargs
-        )
-        # drop indices to avoid potential race condition with auto region
-        if region_was_autodetected:
-            dataset = dataset.drop_vars(dataset.indexes)
+        region = _validate_and_autodetect_region(dataset, region, mode, open_kwargs)
+        # can't modify indexed with region writes
+        dataset = dataset.drop_vars(dataset.indexes)
         if append_dim is not None and append_dim in region:
             raise ValueError(
                 f"cannot list the same dimension in both ``append_dim`` and "
diff --git a/xarray/tests/test_backends.py b/xarray/tests/test_backends.py
index 3fb137977e8..5d2fefecf48 100644
--- a/xarray/tests/test_backends.py
+++ b/xarray/tests/test_backends.py
@@ -13,12 +13,12 @@
 import tempfile
 import uuid
 import warnings
-from collections.abc import Generator, Iterator
+from collections.abc import Generator, Iterator, Mapping
 from contextlib import ExitStack
 from io import BytesIO
 from os import listdir
 from pathlib import Path
-from typing import TYPE_CHECKING, Any, Final, cast
+from typing import TYPE_CHECKING, Any, Final, Literal, cast
 from unittest.mock import patch
 
 import numpy as np
@@ -5641,24 +5641,27 @@ def test_zarr_region_index_write(self, tmp_path):
             }
         )
 
-        ds_region = 1 + ds.isel(x=slice(2, 4), y=slice(6, 8))
+        region_slice = dict(x=slice(2, 4), y=slice(6, 8))
+        ds_region = 1 + ds.isel(region_slice)
 
         ds.to_zarr(tmp_path / "test.zarr")
 
-        with patch.object(
-            ZarrStore,
-            "set_variables",
-            side_effect=ZarrStore.set_variables,
-            autospec=True,
-        ) as mock:
-            ds_region.to_zarr(tmp_path / "test.zarr", region="auto", mode="r+")
-
-            # should write the data vars but never the index vars with auto mode
-            for call in mock.call_args_list:
-                written_variables = call.args[1].keys()
-                assert "test" in written_variables
-                assert "x" not in written_variables
-                assert "y" not in written_variables
+        region: Mapping[str, slice] | Literal["auto"]
+        for region in [region_slice, "auto"]:  # type: ignore
+            with patch.object(
+                ZarrStore,
+                "set_variables",
+                side_effect=ZarrStore.set_variables,
+                autospec=True,
+            ) as mock:
+                ds_region.to_zarr(tmp_path / "test.zarr", region=region, mode="r+")
+
+                # should write the data vars but never the index vars with auto mode
+                for call in mock.call_args_list:
+                    written_variables = call.args[1].keys()
+                    assert "test" in written_variables
+                    assert "x" not in written_variables
+                    assert "y" not in written_variables
 
     def test_zarr_region_append(self, tmp_path):
         x = np.arange(0, 50, 10)