St. Louis County is located in the eastern-central portion of Missouri. It is bounded by the City of St. Louis and the Mississippi River to the east, the Missouri River to the north, and the Meramec River to the south. At the 2020 census, the total population was 1,004,125, making it the most populous county in Missouri. Its county seat is Clayton. The county is included in the St. Louis, MO–IL metropolitan statistical area.

The Meramec River, sometimes spelled Maramec River, is one of the longest free-flowing waterways in the U.S. state of Missouri, draining 3,980 square miles (10,300 km2) while wandering 218 miles (351 km) from headwaters southeast of Salem to where it empties into the Mississippi River near St. Louis at Arnold and Oakville. The Meramec watershed covers six Missouri Ozark Highland counties—Dent, Phelps, Crawford, Franklin, Jefferson, and St. Louis—and portions of eight others—Maries, Gasconade, Iron, Washington, Reynolds, St. Francois, Ste. Genevieve, and Texas. Between its source and its mouth, it falls 1,025 feet (312 m). Year-round navigability begins above Maramec Spring, just south of St. James. The Meramec's size increases at the confluence of the Dry Fork, and its navigability continues until the river enters the Mississippi at Arnold, Missouri.