diff --git a/doc/source/whatsnew/v1.5.2.rst b/doc/source/whatsnew/v1.5.2.rst
index dd909415d9e85..4654b7630c882 100644
--- a/doc/source/whatsnew/v1.5.2.rst
+++ b/doc/source/whatsnew/v1.5.2.rst
@@ -27,7 +27,7 @@ Fixed regressions
 Bug fixes
 ~~~~~~~~~
 - Bug in the Copy-on-Write implementation losing track of views in certain chained indexing cases (:issue:`48996`)
--
+- Fixed memory leak in :meth:`.Styler.to_excel` (:issue:`49751`)
 
 .. ---------------------------------------------------------------------------
 .. _whatsnew_152.other:
diff --git a/pandas/io/formats/excel.py b/pandas/io/formats/excel.py
index a26b85390fd49..1c2aa8f4262f6 100644
--- a/pandas/io/formats/excel.py
+++ b/pandas/io/formats/excel.py
@@ -170,10 +170,13 @@ def __init__(self, inherited: str | None = None) -> None:
             self.inherited = self.compute_css(inherited)
         else:
             self.inherited = None
+        # We should avoid lru_cache on the __call__ method.
+        # Otherwise once the method __call__ has been called
+        # garbage collection no longer deletes the instance.
+        self._call_cached = lru_cache(maxsize=None)(self._call_uncached)
 
     compute_css = CSSResolver()
 
-    @lru_cache(maxsize=None)
     def __call__(
         self, declarations: str | frozenset[tuple[str, str]]
     ) -> dict[str, dict[str, str]]:
@@ -193,6 +196,11 @@ def __call__(
             A style as interpreted by ExcelWriter when found in
             ExcelCell.style.
         """
+        return self._call_cached(declarations)
+
+    def _call_uncached(
+        self, declarations: str | frozenset[tuple[str, str]]
+    ) -> dict[str, dict[str, str]]:
         properties = self.compute_css(declarations, self.inherited)
         return self.build_xlstyle(properties)
 
diff --git a/pandas/tests/io/formats/test_to_excel.py b/pandas/tests/io/formats/test_to_excel.py
index 7481baaee94f6..2a0f9f59972ef 100644
--- a/pandas/tests/io/formats/test_to_excel.py
+++ b/pandas/tests/io/formats/test_to_excel.py
@@ -357,7 +357,7 @@ def test_css_excel_cell_precedence(styles, expected):
     """It applies favors latter declarations over former declarations"""
     # See GH 47371
     converter = CSSToExcelConverter()
-    converter.__call__.cache_clear()
+    converter._call_cached.cache_clear()
     css_styles = {(0, 0): styles}
     cell = CssExcelCell(
         row=0,
@@ -369,7 +369,7 @@ def test_css_excel_cell_precedence(styles, expected):
         css_col=0,
         css_converter=converter,
     )
-    converter.__call__.cache_clear()
+    converter._call_cached.cache_clear()
 
     assert cell.style == converter(expected)
 
@@ -410,7 +410,7 @@ def test_css_excel_cell_cache(styles, cache_hits, cache_misses):
     """It caches unique cell styles"""
     # See GH 47371
     converter = CSSToExcelConverter()
-    converter.__call__.cache_clear()
+    converter._call_cached.cache_clear()
 
     css_styles = {(0, i): _style for i, _style in enumerate(styles)}
     for css_row, css_col in css_styles:
@@ -424,8 +424,8 @@ def test_css_excel_cell_cache(styles, cache_hits, cache_misses):
             css_col=css_col,
             css_converter=converter,
         )
-    cache_info = converter.__call__.cache_info()
-    converter.__call__.cache_clear()
+    cache_info = converter._call_cached.cache_info()
+    converter._call_cached.cache_clear()
 
     assert cache_info.hits == cache_hits
     assert cache_info.misses == cache_misses
diff --git a/pyproject.toml b/pyproject.toml
index 1ccf577538db7..2c032fd4d8dea 100644
--- a/pyproject.toml
+++ b/pyproject.toml
@@ -134,7 +134,6 @@ disable = [
   "invalid-envvar-default",
   "invalid-overridden-method",
   "keyword-arg-before-vararg",
-  "method-cache-max-size-none",
   "non-parent-init-called",
   "overridden-final-method",
   "pointless-statement",