diff --git a/doc/source/whatsnew/v2.1.0.rst b/doc/source/whatsnew/v2.1.0.rst
index 7b9efd7f593dd..b3f17c62f3dde 100644
--- a/doc/source/whatsnew/v2.1.0.rst
+++ b/doc/source/whatsnew/v2.1.0.rst
@@ -295,6 +295,7 @@ Deprecations
 - Deprecated allowing ``downcast`` keyword other than ``None``, ``False``, "infer", or a dict with these as values in :meth:`Series.fillna`, :meth:`DataFrame.fillna` (:issue:`40988`)
 - Deprecated allowing arbitrary ``fill_value`` in :class:`SparseDtype`, in a future version the ``fill_value`` will need to be compatible with the ``dtype.subtype``, either a scalar that can be held by that subtype or ``NaN`` for integer or bool subtypes (:issue:`23124`)
 - Deprecated behavior of :func:`assert_series_equal` and :func:`assert_frame_equal` considering NA-like values (e.g. ``NaN`` vs ``None`` as equivalent) (:issue:`52081`)
+- Deprecated bytes input to :func:`read_excel`. To read a file path, use a string or path-like object. (:issue:`53767`)
 - Deprecated constructing :class:`SparseArray` from scalar data, pass a sequence instead (:issue:`53039`)
 - Deprecated falling back to filling when ``value`` is not specified in :meth:`DataFrame.replace` and :meth:`Series.replace` with non-dict-like ``to_replace`` (:issue:`33302`)
 - Deprecated literal json input to :func:`read_json`. Wrap literal json string input in ``io.StringIO`` instead. (:issue:`53409`)
@@ -305,6 +306,7 @@ Deprecations
 - Deprecated the "method" and "limit" keywords on :meth:`Series.fillna`, :meth:`DataFrame.fillna`, :meth:`SeriesGroupBy.fillna`, :meth:`DataFrameGroupBy.fillna`, and :meth:`Resampler.fillna`, use ``obj.bfill()`` or ``obj.ffill()`` instead (:issue:`53394`)
 - Deprecated the ``method`` and ``limit`` keywords in :meth:`DataFrame.replace` and :meth:`Series.replace` (:issue:`33302`)
 - Deprecated values "pad", "ffill", "bfill", "backfill" for :meth:`Series.interpolate` and :meth:`DataFrame.interpolate`, use ``obj.ffill()`` or ``obj.bfill()`` instead (:issue:`53581`)
+-
 
 .. ---------------------------------------------------------------------------
 .. _whatsnew_210.performance:
diff --git a/pandas/io/excel/_base.py b/pandas/io/excel/_base.py
index f4782dcfcc08d..fbc3893e9b53a 100644
--- a/pandas/io/excel/_base.py
+++ b/pandas/io/excel/_base.py
@@ -21,6 +21,7 @@
     cast,
     overload,
 )
+import warnings
 import zipfile
 
 from pandas._config import config
@@ -36,6 +37,7 @@
     Appender,
     doc,
 )
+from pandas.util._exceptions import find_stack_level
 from pandas.util._validators import check_dtype_backend
 
 from pandas.core.dtypes.common import (
@@ -97,6 +99,10 @@
     By file-like object, we refer to objects with a ``read()`` method,
     such as a file handle (e.g. via builtin ``open`` function)
     or ``StringIO``.
+
+    .. deprecated:: 2.1.0
+        Passing byte strings is deprecated. To read from a
+        byte string, wrap it in a ``BytesIO`` object.
 sheet_name : str, int, list, or None, default 0
     Strings are used for sheet names. Integers are used in zero-indexed
     sheet positions (chart sheets do not count as a sheet position).
@@ -1504,6 +1510,13 @@ def __init__(
         # First argument can also be bytes, so create a buffer
         if isinstance(path_or_buffer, bytes):
             path_or_buffer = BytesIO(path_or_buffer)
+            warnings.warn(
+                "Passing bytes to 'read_excel' is deprecated and "
+                "will be removed in a future version. To read from a "
+                "byte string, wrap it in a `BytesIO` object.",
+                FutureWarning,
+                stacklevel=find_stack_level(),
+            )
 
         # Could be a str, ExcelFile, Book, etc.
         self.io = path_or_buffer
diff --git a/pandas/tests/io/excel/test_readers.py b/pandas/tests/io/excel/test_readers.py
index 88f55145b599a..1e17e866ec530 100644
--- a/pandas/tests/io/excel/test_readers.py
+++ b/pandas/tests/io/excel/test_readers.py
@@ -3,6 +3,7 @@
     time,
 )
 from functools import partial
+from io import BytesIO
 import os
 from pathlib import Path
 import platform
@@ -873,7 +874,7 @@ def test_corrupt_bytes_raises(self, engine):
             error = BadZipFile
             msg = "File is not a zip file"
         with pytest.raises(error, match=msg):
-            pd.read_excel(bad_stream)
+            pd.read_excel(BytesIO(bad_stream))
 
     @pytest.mark.network
     @tm.network(
@@ -1446,6 +1447,18 @@ def test_euro_decimal_format(self, read_ext):
 
 
 class TestExcelFileRead:
+    def test_deprecate_bytes_input(self, engine, read_ext):
+        # GH 53830
+        msg = (
+            "Passing bytes to 'read_excel' is deprecated and "
+            "will be removed in a future version. To read from a "
+            "byte string, wrap it in a `BytesIO` object."
+        )
+
+        with tm.assert_produces_warning(FutureWarning, match=msg):
+            with open("test1" + read_ext, "rb") as f:
+                pd.read_excel(f.read(), engine=engine)
+
     @pytest.fixture(autouse=True)
     def cd_and_set_engine(self, engine, datapath, monkeypatch):
         """
@@ -1629,7 +1642,7 @@ def test_excel_read_binary(self, engine, read_ext):
         with open("test1" + read_ext, "rb") as f:
             data = f.read()
 
-        actual = pd.read_excel(data, engine=engine)
+        actual = pd.read_excel(BytesIO(data), engine=engine)
         tm.assert_frame_equal(expected, actual)
 
     def test_excel_read_binary_via_read_excel(self, read_ext, engine):