Greenville is a small, fourth-class city located on U.S. Highway 67 near the intersection with Route D and E in Wayne County, Missouri in the United States along the St. Francis River. As of the 2000 U.S. Census, the city's population was 451; a 2003 estimate, however, showed the population to be 444. Greenville was incorporated and founded as the county seat of Wayne County in 1819.