Charleston is a city in Mississippi County, Missouri, United States. The population was 4,732 at the 2000 census. It is the county seat of Mississippi County.
Charleston is the biggest town on the Missouri side near the confluence of the Mississippi River and Ohio River at Bird's Point, Missouri (11 miles east on U.S. Route 60). Its history has been tied to traffic on the rivers.
Settlement initially occurred on the north side in what in 1805 was called Matthews Prairie.