The county was named for former General and United States Senator Thomas Sumter (1734–1832) of South Carolina.

By the 1850 census, the demographic makeup of the county had become 6,469 whites, 3,835 enslaved African Americans, and 18 free people of color.

During the American Civil War (1861–65), the small village named Andersonville, 9 mi (14 km) north of Americus on the county's northern edge, was selected by Confederate authorities as the site for a prisoner-of-war camp.

The 495-acre (2.00 km2) park lies in both Macon and Sumter Counties and consists of the historic prison site and the National Cemetery, which originally was reserved for the Union dead.

Jimmy Carter was born and raised on a peanut farm in Plains, a small community on the county's western edge.

The headquarters of Habitat for Humanity International, a nonprofit organization whose mission is to eliminate homelessness, is located in Americus, the home of its founder, Millard Fuller.

South Georgia Technical College, which stands near Souther Field, was a training base for American and British aviators during World War I (1917–18).

Charles Lindbergh learned to fly here and assembled a military surplus "Jenny" aircraft with the help of mechanics at Souther Field.

Downtown Americus boasts two prominent examples of historic restoration: the Windsor Hotel, built in 1892, and the Rylander Theatre, which originally opened in 1921.

Its major employers include Cooper Lighting, Georgia Southwestern State University, Magnolia Manor, Phoebe Sumter Medical Center, and Walmart.