Mayersville is a town upon the east bank of the Mississippi River, and the county seat for Issaquena County, Mississippi, United States. It is located in the Mississippi Delta region, known for cotton cultivation in the antebellum era. Once the trading middle for the county, the town was superseded considering railroads were built into the area. The population of the majority-black town was 547 at the 2010 census, down from 795 at the 2000 census.

Native Americans had lived in this Place since archaic times. The Mayersville Archeological Site, added to the National Register of Historic Places in 1980, is upon privately owned land. It contains the remains of earthwork mounds build up primarily in the Mayersville phase (
AD 1200–1400) of the earlier Mississippian culture.

A 1950 survey by Philip Phillips of the Peabody Museum of Archaeology and Ethnology reported eleven ancient mounds. By the grow old the site was nominated by the own up to the National Register of Historic Places, two mounds had been unconditionally destroyed, a third one was approximately gone, three were edited in size by plowing, and five remained nearly as described. Three mounds had enclosed a large plaza measuring in bank account to 560 by 790 feet (170 by 240 m). The fourth side was bounded by three mounds. Among these was Mound I, which was found to have been re-occupied from 1400 to 1600, perhaps by the succeeding Choctaw people. A European-American family cemetery associated with a 19th-century plantation was developed on Mound A.

The first autograph album of non-Native deal was in 1830, when European-American Ambrose Gipson purchased a large body of estate along the Mississippi River and founded “Gipson’s Landing”. This soon became the port on the river for shipping out the cotton of Issaquena and Sharkey counties. It attracted changing populations of river crews, gamblers, and traders, as with ease as enactment boats during low water times. The shipping chronicles for David Mayer, who owned open Mout Level Plantation, show that river freight was shipped from the harbor via steamboat to points in Arkansas, Louisiana, Missouri, and Mississippi.