Mayersville is a town located on the east bank of the Mississippi River in the state of Mississippi, United States. It serves as the county seat for Issaquena County and is situated within the Mississippi Delta region.
Historically, the area was recognized for its cotton cultivation during the antebellum era. While Mayersville once functioned as the primary trading center for the county, it was eventually superseded by other locations following the construction of railroads in the region. As of the 2020 census, the town had a population of 433.