Issaquena County Mississippi has 4 places on the National Register of Historic Places including 1 place of National significance and 2 places of Statewide significance. Significant places include Mayersville Archeological Site, Aden Site (22Is509;22M3) and Grace Archeological Site, Railroad Section Foreman's House.
Prehistoric cultural affiliation(s) include Late Woodland, Early Woodland, Mississippian and Mayersville Phase dating back to 6999 BC. Prominent architectural styles found in Issaquena Country are .