In 1996, it became the first district in which a Wisconsin state legislator was successfully removed from office via recall election, when Kimberly Plache defeated George Petak.

[6] As with all state senate and assembly seats, the boundaries of the 21st have moved over time during decennial redistricting.

The district was created after the 1850 census and reapportionment and was drawn for Winnebago County, in central Wisconsin.

In redistricting after the 2010 census, the city of Racine was mostly removed and rural and suburban portions of Kenosha County were added to the district, turning the 21st into a safe Republican seat.

The 21st senate district has had several notable officeholders, including American Civil War General John Azor Kellogg and Wisconsin Governors Coles Bashford and Walter Samuel Goodland.