Wayne County is located in southeast Missouri near St Louis.. It has an estimated population size 26 , 912 people ( 2020 ) . The largest city , Greenville , serves as its county seat . Primary revenue sources come from both agricultural production including crops such as tobacco , corn , cotton etc., & small businesses mostly related to leathergoods production . Tourism has been another important sector due to its proximity to several historical sites & natural attractions like Big Creek State Park & Mark Twain National Forest .