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St. Louis () is the second-largest city in Missouri. It sits near the confluence of the Mississippi and the Missouri Rivers. In 2020, the city proper had a population of 301,578, while the bi-state metropolitan area, which extends into Illinois, had an estimated population of over 2.8 million, making it the largest metropolitan area in Missouri, the second-largest in Illinois, and the 20th-largest in the United States.

Before European settlement, the area was a regional center of Native American Mississippian culture. St. Louis was founded on February 14, 1764, by French fur traders Gilbert Antoine de St. Maxent, Pierre Laclède and Auguste Chouteau, who named it for Louis IX of France. In 1764, following France's defeat in the Seven Years' War, the area was ceded to Spain. In 1800, it was retroceded to France, which sold it three years later to the United States as part of the Louisiana Purchase; the city was then the point of embarkation for the Corps of Discovery on the Lewis and Clark Expedition. In the 19th century, St. Louis became a major port on the Mississippi River; from 1870 until the 1920 census, it was the fourth-largest city in the country. It separated from St. Louis County in 1877, becoming an independent city and limiting its political boundaries. In 1904, it hosted the Louisiana Purchase Exposition and the Summer Olympics.

A "Gamma" global city with a metropolitan GDP of more than $160 billion in 2017, metropolitan St. Louis has a diverse economy with strengths in the service, manufacturing, trade, transportation, and tourism industries. It is home to eight Fortune 500 companies. Major companies headquartered or with significant operations in the city include Ameren Corporation, Peabody Energy, Nestlé Purina PetCare, Anheuser-Busch, Wells Fargo Advisors, Stifel Financial, Spire, Inc., MilliporeSigma, FleishmanHillard, Square, Inc., U.S. Bank, Anthem BlueCross and Blue Shield, Federal Reserve Bank of St. Louis, U.S. Department of Agriculture, National Geospatial-Intelligence Agency, Centene Corporation, and Express Scripts.

Major research universities include Saint Louis University and Washington University in St. Louis. The Washington University Medical Center in the Central West End neighborhood hosts an agglomeration of medical and pharmaceutical institutions, including Barnes-Jewish Hospital.

St. Louis has four professional sports teams: the St. Louis Cardinals of Major League Baseball, the St. Louis Blues of the National Hockey League, St. Louis City SC of Major League Soccer, anticipated to begin play in 2023, and the St. Louis BattleHawks of the XFL. Among the city's notable sights is the 630-foot (192 m) Gateway Arch in Downtown St. Louis, the St. Louis Zoo, the Missouri Botanical Garden, the Saint Louis Art Museum, and Bellefontaine Cemetery and Arboretum.