Charleston is a city in Mississippi County, Missouri, United States. The population was 5,056 at the 2020 census, a decrease from 5,947 in 2…Charleston is a city in Mississippi County, Missouri, United States. The population was 5,056 at the 2020 census, a decrease from 5,947 in 2010. It is the county seat of Mississippi County and since 1968 has been home to the annual Dogwood-Azalea Festival which highlights the old homes and gardens throughout the town.