The 21st district was created by the 1850 Michigan Constitution, as the 1835 constitution only permitted a maximum of eight senate districts.

[2][3] It has been represented by Democrat Sarah Anthony since 2023.

[5] District 21, as dictated by the 2011 Apportionment Plan, covered Berrien, Cass, and St. Joseph Counties in far southwest Michigan.

Communities in the district included Benton Harbor, Niles, St. Joseph, Buchanan, Benton Heights, Fair Plain, Paw Paw Lake, Dowagiac, Sturgis, Three Rivers, Benton Township, Lincoln Township, Niles Township, and St. Joseph Township.

[7] It bordered the state of Indiana, as well as Lake Michigan.