Cuthbert was named for Colonel John Alfred Cuthbert, editor, congressman, and judge. The city is the county seat of Randolph County and was incorporated on December 26, 1831.

Cuthbert is home to Andrew College, a private Methodist college that was the second in the nation to grant degrees to women. This college served as a Confederate hospital during the Civil War. In Cuthbert's Greenwood Cemetery are the graves of twenty-four Confederate soldiers who died at Hood Hospital. These soldiers are commemorated with a life-sized full figure marble sculpture of a confederate soldier.