David E. Twiggs (1790–1862), US soldier during the War of 1812 and Mexican War, and a general in the Confederate States Army during the American Civil War
Chuck Leavell, an American musician and current tree farmer in Twiggs County, Georgia, who was a member of The Allman Brothers Band during the height of their 1970's popularity, a founding member of the jazz-rock combo Sea Level, a frequently-employed session musician, and long-time touring member of The Rolling Stones.