St. Louis was founded in 1764 just south of the confluence of the Missouri and Mississippi rivers by colonial French traders Pierre Laclède and René Auguste Chouteau, who named the settlement after King Louis IX of France. The city, as well as the future state of Missouri, became part of the Spanish Empire after the French were defeated in the Seven Years' War. In 1800, the land was secretly transferred back to France, whose leader, Napoleon Bonaparte, sold it to the United States in 1803. Nicknamed the "Gateway to the West" for its role in the westward expansion of the United States, the city gave the moniker in 1965 to the new Gateway Arch built as part of the Jefferson National Expansion Memorial; the arch has become the iconic image of St. Louis.

Once the 4th-largest U.S. city, St. Louis proper has seen its population slip to 52nd.[9] At the peak of the city's influence, St. Louis hosted the 1904 World's Fair and 1904 Olympic Games, both the first of their kind held in the Western Hemisphere.