Mayersville is a town in Issaquena County, Mississippi, United States. The population was 795 at the 2000 census. The town was named for David Mayer, on whose plantation the town was built. It is the county seat of Issaquena County. One of its more famous natives is Unita Blackwell, Mississippi's first black female mayor, who was elected in 1977. She became president of the U.S. National Conference of Black Mayors.
Mayersville is located at 32°54′4″N 91°3′2″W / 32.90111°N 91.05056°W / 32.90111; -91.05056 (32.901179, -91.050585).
According to the United States Census Bureau, the town has a total area of 1.1 square miles (2.9 km²), none of which is covered by water.