Missouri's recorded history begins in the latter half of the 17th cent. when the French explorers Jacques Marquette and Louis Jolliet descended the Mississippi River, followed by Robert Cavelier, sieur de La Salle, who claimed the whole area drained by the Mississippi River for France, calling the territory Louisiana. When the French explorers arrived the area was inhabited by Native Americans of the Osage and the Missouri groups, and by the end of the 17th cent. French trade with the Native Americans flourished.

In the early 18th cent. the French worked the area's lead mines and made numerous trips through Missouri in search of furs. Trade down the Mississippi prompted the settlement of Ste. Geneviève about 1735 and the founding of St. Louis in 1764 by Pierre Laclede and René Auguste Chouteau, who were both in the fur-trading business. Although not involved in the last conflict (1754–63) of the French and Indian Wars, Missouri was affected by the French defeat when, in 1762, France secretly ceded the territory west of the Mississippi to Spain. In 1800 the Louisiana Territory (including the Missouri area) was retroceded to France, but in 1803 it passed to the United States as part of the Louisiana Purchase.

French influence remained dominant, even though by this time Americans had filtered into the territory, particularly to the lead mines at Ste Geneviève and Potosi. By the time of the Lewis and Clark expedition (1803–6), St. Louis was already known as the gateway to the Far West.

The U.S. Territory of Missouri was set up in 1812, but settlement was slow even after the War of 1812. The coming of the steamboat increased traffic and trade on the Mississippi, and settlement progressed. Planters from the South had introduced slavery into the territory, but their plantations were restricted to a small area. However, the question of admitting the Missouri Territory as a state became a burning national issue because it involved the question of extending slavery into the territories. The dispute was resolved by the Missouri Compromise, which admitted (1821) Missouri to the Union as a slave state but excluded slavery from lands of the Louisiana Purchase north of lat. 36°30′N. (All of Missouri lies north of 36°30′ except for the southeastern bootheel.)

Slaveholding interests became politically powerful, but the state remained principally a fur-trading center. In 1822, W. H. Ashley (who later made a fortune in fur trading) led an expedition of the adventurous trappers who became known as mountain men up the Missouri River to explore the West for furs. From Missouri traders established a thriving commerce over the Santa Fe Trail with the inhabitants of New Mexico, and pioneers followed the Oregon Trail to settle the Northwest. Franklin, Westport, Independence, and St. Joseph became famous as the points of origin of these expeditions.

Settlement of Missouri itself quickened, spreading in the 1820s over the river valleys into central Missouri and by the 1830s into W Missouri. The boundaries of the state were formed after Native Americans gave up their claim to Platte co. in 1836; this strip of land in the northwest corner of Missouri was added to the state. Mormon immigrants came to settle Missouri in the 1830s, but their opposition to slavery and their growing numbers made them unwelcome and they were driven from the state in 1839. German immigrants, however, were cordially received during the 1840s and 50s, settling principally in the St. Louis area.

In 1854 the problem of slavery was made acute with the passage of the Kansas-Nebraska Act, leaving the question of slavery in the Kansas and Nebraska territories to the settlers themselves. The proslavery forces in Missouri became very active in trying to win Kansas for the slave cause and contributed to the violence and disorder that tore the territory apart in the years just prior to the Civil War. Nevertheless Missouri also had leaders opposed to slavery, including one of its Senators, Thomas Hart Benton.

During the Civil War most Missourians remained loyal to the federal government. A state convention that met in Mar., 1861, voted against secession, and in 1862 the convention set up a provisional government. Guerrilla activities persisted during this period, and the lawlessness bred by civil warfare persisted in Missouri after the war in the activities of outlaws such as Jesse James.

A new Missouri rose out of the war—the semi-Southern atmosphere, along with the river life and steamboating, began to decline, but the flavor of the period was preserved in the works of one of Missouri's most celebrated sons, Mark Twain. The coming of the railroads brought the eventual decay of many of Missouri's river towns and tied the state more closely to the East and North. Urbanization and industrialization progressed, and the Louisiana Purchase Exposition, held at St. Louis in 1904, dramatically revealed Missouri's economic growth.

Since the brief period of radical Republican rule from 1864 to 1870, Missouri has been permanently wedded to neither major party. While tending toward the Republicans in the days of Theodore Roosevelt, it turned solidly Democratic for Franklin D. Roosevelt and helped to elect Missourian Harry S. Truman to the presidency in 1948. Political machines in the large cities have attracted national attention, notably the machine of Thomas J. Pendergast (1872–1945) in Kansas City. Missouri has contributed to the United States such outstanding statesmen as Champ Clark, James Reed, and W. Stuart Symington. Thomas Hart Benton, a descendant of the Missouri Senator of the same name, was one of the country's important artists.

Although during World War I general prosperity prevailed in the state, the depression years of the 1930s sent farm values crashing, and many banks, especially in rural areas, failed. Prosperity returned during World War II, when both St. Louis and Kansas City served as vital transportation centers, and industrialization increased enormously. In the postwar period, Missouri became the second largest producer (behind Michigan) of automobiles in the nation. Although most industry remains based in the two metropolitan centers, smaller Missouri communities, especially suburbs, have since attracted much light and heavy industry, as well as former city dwellers. St. Louis lost half its population between 1950 to 1990, and out-migration has continued; what was once the fourth largest U.S. city is now barely in the top 50 in size.

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