Charleston is a city in Mississippi County, Missouri, United States. The population was 5,056 at the 2020 census, down from 5,947 in 2010. I…Charleston is a city in Mississippi County, Missouri, United States. The population was 5,056 at the 2020 census, down from 5,947 in 2010. It is the county seat of Mississippi County and is home to the Southeast Correctional Center.