Hernando De Soto visited the Missouri area in 1541. France's claim to the entire region was based on Sieur de la Salle's travels in 1682. French fur traders established Ste. Genevieve in 1735, and St. Louis was first settled in 1764.

The U.S. gained Missouri from France as part of the Louisiana Purchase in 1803, and the territory was admitted as a state following the Missouri Compromise of 1820. Throughout the pre–Civil War period and during the war, Missourians were sharply divided in their opinions about slavery and in their allegiances, supplying both Union and Confederate forces with troops. However, the state itself remained in the Union.

Historically, Missouri played a leading role as a gateway to the West, St. Joseph being the eastern starting point of the Pony Express, while the much-traveled Santa Fe and Oregon trails began in Independence.

Missouri's economy is highly diversified. Service industries provide more income and jobs than any other segment, and include a growing tourism and travel sector. Wholesale and retail trade, manufacturing, and agriculture also play significant roles in the state's economy.

Missouri is a leading producer of transportation equipment (including automobile manufacturing and auto parts), beer and beverages, and defense and aerospace technology. Food processing is the state's fastest-growing industry.

Missouri mines produce 90% of the nation's principal (non-recycled) lead supply. Other natural resources include iron ore, zinc, barite, limestone, and timber.

The state's top agricultural products include grain, sorghum, hay, corn, soybeans, and rice. Missouri also ranks high among the states in cattle and calves, hogs, and turkeys and broilers. A vibrant wine industry also contributes to the economy.

Tourism draws hundreds of thousands of visitors to a number of Missouri points of interest: the country-music shows of Branson; Bass Pro Shops national headquarters (Springfield); the Gateway Arch at the Jefferson National Expansion (St. Louis); Mark Twain's boyhood home (Hannibal); the Harry S Truman home and library (Independence); the scenic beauty of the Ozark National Scenic Riverways; and the Pony Express and Jesse James museums (St. Joseph). The state's different lake regions also attract fishermen and sun-seekers from throughout the Midwest.