city, seat of St. Charles county, eastern Missouri, U.S., on bluffs overlooking the Missouri River, there bridged to St. Louis, 22 miles (35 km) southeast. One of the earliest settlements on the Missouri, it was founded in 1769 by Louis Blanchette as Les Petites Côtes (“The Little Hills”). The site, transferred to Spain in 1770, was dedicated in 1791 as the village of San Carlos Borromeo after a church of that name was built there. In May 1804 Meriwether Lewis and William Clark began their westward expedition from San Carlos, the name of which was anglicized to St. Charles upon their return in 1806. It was the state's first capital (1821–26), and the First Missouri State Capitol is preserved.

A trade and shipping centre for farm produce (primarily wheat, corn 【maize】, and oats), St. Charles also has some manufactures (missiles and metal products) and tourism. It is the seat of Lindenwood University (four coordinated colleges originating in 1827 with the first women's college west of the Mississippi) and of the Convent of the Sacred Heart (1818; likewise the first free school). Frontiersman Daniel Boone's last home is nearby. Inc. village, 1809; city, 1849. Pop. (2000) 60,321; (2005 est.) 62,304.