diff --git a/doc/source/whatsnew/v0.25.0.rst b/doc/source/whatsnew/v0.25.0.rst
index 276812a564e03..1a0df4789f4c7 100644
--- a/doc/source/whatsnew/v0.25.0.rst
+++ b/doc/source/whatsnew/v0.25.0.rst
@@ -466,6 +466,7 @@ I/O
 - Fixed memory leak in :meth:`DataFrame.to_json` when dealing with numeric data (:issue:`24889`)
 - Bug in :func:`read_json` where date strings with ``Z`` were not converted to a UTC timezone (:issue:`26168`)
 - Added ``cache_dates=True`` parameter to :meth:`read_csv`, which allows to cache unique dates when they are parsed (:issue:`25990`)
+- :meth:`DataFrame.to_excel` now raises a ``ValueError`` when the caller's dimensions exceed the limitations of Excel (:issue:`26051`)
 
 Plotting
 ^^^^^^^^
diff --git a/pandas/io/formats/excel.py b/pandas/io/formats/excel.py
index fd6e3304ec4ef..4db00e34b39e2 100644
--- a/pandas/io/formats/excel.py
+++ b/pandas/io/formats/excel.py
@@ -341,6 +341,9 @@ class ExcelFormatter:
         This is only called for body cells.
     """
 
+    max_rows = 2**20
+    max_cols = 2**14
+
     def __init__(self, df, na_rep='', float_format=None, cols=None,
                  header=True, index=True, index_label=None, merge_cells=False,
                  inf_rep='inf', style_converter=None):
@@ -648,6 +651,13 @@ def write(self, writer, sheet_name='Sheet1', startrow=0,
         from pandas.io.excel import ExcelWriter
         from pandas.io.common import _stringify_path
 
+        num_rows, num_cols = self.df.shape
+        if num_rows > self.max_rows or num_cols > self.max_cols:
+            raise ValueError("This sheet is too large! Your sheet size is: " +
+                             "{}, {} ".format(num_rows, num_cols) +
+                             "Max sheet size is: {}, {}".
+                             format(self.max_rows, self.max_cols))
+
         if isinstance(writer, ExcelWriter):
             need_save = False
         else:
diff --git a/pandas/tests/io/test_excel.py b/pandas/tests/io/test_excel.py
index 100de227aa97c..7fe8e1d18838f 100644
--- a/pandas/tests/io/test_excel.py
+++ b/pandas/tests/io/test_excel.py
@@ -1185,6 +1185,24 @@ class and any subclasses, on account of the `autouse=True`
 class TestExcelWriter(_WriterBase):
     # Base class for test cases to run with different Excel writers.
 
+    def test_excel_sheet_size(self):
+
+        # GH 26080
+        breaking_row_count = 2**20 + 1
+        breaking_col_count = 2**14 + 1
+        # purposely using two arrays to prevent memory issues while testing
+        row_arr = np.zeros(shape=(breaking_row_count, 1))
+        col_arr = np.zeros(shape=(1, breaking_col_count))
+        row_df = pd.DataFrame(row_arr)
+        col_df = pd.DataFrame(col_arr)
+
+        msg = "sheet is too large"
+        with pytest.raises(ValueError, match=msg):
+            row_df.to_excel(self.path)
+
+        with pytest.raises(ValueError, match=msg):
+            col_df.to_excel(self.path)
+
     def test_excel_sheet_by_name_raise(self, *_):
         import xlrd