St. Francois County is a county located in the Lead Belt region in the U.S. state of Missouri. As of the 2010 census, the population was 65,359. The largest city and county seat is Farmington. The county was officially organized on December 19, 1821. It was named after the St. Francis River. The origin of the river's name is unclear. It might refer to St. Francis of Assisi. Another possibility is that Jacques Marquette, a Jesuit who explored the region in 1673, named the river for the Jesuit missionary Francis Xavier. Marquette had spent some time at the mission of St. Francois Xavier before his voyage and, as a Jesuit, was unlikely to have given the river a name honoring the Franciscans.