Macon County is named in honor of General Nathaniel Macon, a North Carolina statesman and president pro tempore of the U.S. Senate. Macon County was carved from Houston and Marion counties in 1837.

Andersonville National Cemetery and Park is in the southwest tip of Macon County. Approximately 45,000 Union soldiers were imprisoned here during the Civil War, with 13,000 perishing from hunger and disease.

The city of Montezuma was named for the Aztec leader by soldiers returning from the Mexican War.

There is a large Mennonite colony in Macon County near Montezuma.

The Colonel Fish's House is said to be haunted by the ghost of Colonel George Fish after he was found murdered here in the late 1800s. This house was originally located in Oglethorpe and then moved to Americus. The ghost followed the house to its new location.

Sam Henry Rumph of Macon County developed the Elberta Peach, the variety responsible for establishing Georgia as the peach state. John Donald Wade, famous Georgia author, also hails from the county.

Some of the local annual festivals include the Camellia Festival in February, Crepe Myrtle Festival in July, Beaver Creek Festival in the Fall and the Oglethorpe Fall Festival in November.