De Soto is a village in Jackson County, Illinois, United States. The population was 1,653 at the 2000 census. De Soto was largely destroyed by the Great Tri-State Tornado of 1925. Sixty-nine people died in De Soto when approximately 30% of the town was destroyed, and of this total 33 were children at a local school that collapsed from the winds. The tornado affected Missouri, Illinois, and Indiana killing 695 and injuring over 2,000.