De Soto is an unincorporated community in Clarke County, Mississippi. Its altitude is 210 feet (64 m). Desoto was one of four principle towns established in Clarke County before the American Civil War. Established along the Chickasawhay River before the arrival of the Mobile and Ohio Railroad, construction of housing in Desoto may have started as early as 1845 and by 1858 churches were being erected. The town had a Post Office and two churches in 1900 when the population was 258.