De Soto is a city in Jefferson County, Missouri, United States. The population was 6,400 at the 2010 census and is part of the St. Louis metropolitan area. The Van Metre family were first to settle in 1803 .The town was organized in 1857 and is named for the explorer Hernando De Soto, who claimed the Louisiana Territory for Spain. De Soto was the city closest to the mean center of U.S.