Clarke County was formed on December 10, 1812 by the Mississippi Territory. It is named in honor of General John Clarke of Georgia, who was later elected governor of that state.[2] The county had many forts, built by settlers for protection during the Creek War (1813-1814). One of the most notable was Fort Sinquefield.[3]
The first county seat was Clarkesville, formed in 1820. The seat was moved to Macon, later renamed Grove Hill, in 1831. During the American Civil War, the county was notable for its salt production.[2]