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De Soto is a city in Jefferson County, Missouri, United States. The population was 6,449 at the 2020 census and the city is part of the St. Louis metropolitan area. Isaac Van Metre was first to settle in De Soto in the year of 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. population in 1980. The city celebrated its Bicentennial in 2003. The city made national news on and after May 6, 2003, when straight-line winds and a tornado struck the junior high gymnasium.