Greenville is a city located on U.S. Route 67 near the intersection with Route D and E in Wayne County, Missouri, United States, along the …Greenville is a city located on U.S. Route 67 near the intersection with Route D and E in Wayne County, Missouri, United States, along the St. Francis River. The population was 443 at the 2020 census. Greenville was incorporated and founded as the county seat of Wayne County in 1819.