The history of inhabited Missouri may have started as early as 12,000 years ago. Since that time, Missouri has been under the control of several different authorities, including that of various Indian tribes, the Spanish empire, the French empire, and finally the United States.

The first Missourians were descendants of the Asian travelers who crossed the Bering Strait into North America. Nomadic peoples passed  through Missouri in pursuit of game found in the Midwest. Eventually, division of labor and agriculture led to the first settlement of Missouri – the Hopewell people are through to have stayed in the state over 2,000 years ago. These Indian settlements spread throughout Midwest, leaving behind artifacts, mounds, and other evidence of traditions and customs. The first European explorers met up with some of the tribespeople in the 16th century, initially establishing communication and trade between the native Missourians and the European visitors.

The two tribes that dominated present-day Missouri are the Missouri and Osage tribes. The Missouri tribespeople were valuable trading partners for European explorers and settlers, but the relationship was not reciprocal – foreign diseases weakened the tribe. This and increased tensions with enemies led to the decline of the Missouri tribe. The Osage endured longer, however, using much of the state's land for hunting and growing purposes. The Osage also traded with Europeans, but were also eventually displaced by them. In 1808 the Osage ceded control of their land to the United States, and finally left the state for present-day Oklahoma in 1825.

Explorers brought the first knowledge of the Missouri area to the Europeans, who would eventually take control from the native Indians. The first explorer in the area was Spain's Hernando de Soto, whose expedition came upon the area in their survey of the Mississippi River.  De Soto's influence was minimal in comparison to France's Marquette and Jolliet and Robert de la Salle. Marquette's and Jolliet's expedition in the late 17th century provided much geographic  information, which Robert de la Salle used. La Salle established forts and trading posts along the Mississippi, exchanging clothing and food with the natives. La Salle and his followers opened up Missouri to European settlers, including Catholic missionaries and traders, who profoundly influenced the development of the state in their pursuit of Indian converts and animal pelts, respectively.

The French were the ones to discover Missouri's abundance of lead, which proved to be an important factor in Missouri's history. Promise of success in mining operations attracted more European settlers, culminating in the first permanent European settlement at Ste. Genevieve. Although Spain officially took control of the region in 1762 with the Treaty of Fontainbleu, the news did not arrive until after Pierre Laclede Liquest and his company established a post for their grant of exclusive trade in 1764. Laclede's post, St. Louis, survives today as Missouri's second largest city.

The cities and towns started by traders and explorers grew during Spanish rule, and Missouri came to be known as part of the “Louisiana” territory. During Spanish control, the United States came into being following the Revolutionary War, and its citizens slowly spread westward to the Mississippi River. Tensions between these American settlers and the Spanish government over river navigation privileges and early “Manifest Destiny” fervor led to pressure towards and interest in the idea of United States control of Louisiana. Spain's quickly waning power led to the transfer of control of Louisiana to France in 1800. Plagued by war debts, France's ruler Napoleon Bonaparte orchestrated the transfer of Louisiana to its final controller, the United States.

Thomas Jefferson, then-President of the U.S., recognizing the conflicts inherent in European control of Louisiana, including the Mississippi River, persuaded the Congress to make the largest addition to the U.S. ever. In 1803, the Louisiana territory was sold to the United States.

Now owned by the United States, Missouri would later become a distinct territory from the rest of Louisiana. Eventually, after much dispute, it would become a full-fledged state. Like many of the other states, Missouri's road to statehood was paved by conflicts with European powers, recognition of important natural resources, and, unfortunately, displacement of native peoples.

1. The bootheel
   The “bootheel” is the name of the extreme southeast region of Missouri. The bootheel extends about 35 miles into Arkansas. The southern boundary of the heel is a line and the eastern and western boundaries are the Mississippi and St. Francis Rivers, respectively. So-named because it looks like a high-heeled shoe's heel, it contains the parts of Missouri with the lowest altitudes.
2. Hernando de Soto
   Hernando de Soto was a well-known Spanish explorer and nobleman. He is widely credited as the European  “discoverer” of the Mississippi River. He and is crew of 600 men and various livestock came to the Missouri area in 1541, and became the first Europeans to communicate with Missouri's native population. His search for precious metals ended in 1542, when he died next to the river he “discovered.”
3. The culture of the townspeople
   The “townspeople” were a group of Native Americans who lived in the area of present-day St. Louis and Cahokia between 900 and 1500 C.E. The Mississippi River was an important part of their lifestyle – it provided them a place to hunt, fish, and travel. They are known for their pottery, weapons, and art, but most known for their religious rituals. These rituals included the building of “mounds” - the persistence of these symbols makes Cahokia a tourist destination even today.
4. Philippe Renault
   Philippe Renault was the director of the Company of the Indies' mining operations in the Louisiana area in the 1720's. Renault's company mined in Missouri in search for silver, but was only successful in extracting lead. Renault's expansion of the mining industry in Missouri brought settlers to Missouri, and lead remains a Missouri export to this day.
5. Etienne de Bourgmand
   Etienne de Bourgmand was a French  Canadian who most famously traded with the Indians of Missouri and surrounding areas. He and his accompaniment traveled on the Missouri River in 1714, trading and hunting. In 1723 he founded Fort D'Orleans in the northern part of Missouri, and later returned to France.
6. Ste. Genevive
   Ste. Genevive is known for being the first permanent European settlement in Missouri. It was officially founded in 1735, French settlers having been in the area for some time. The area was conducive to settlement – its land supported independent and collective farms, was home to animals valued for their furs and meat, and the earth there could be readily mined for salt and lead.
7. The Pinckney Treaty of 1795
   An important event in the economic history of the Missouri area was the signing of the Pinckney Treaty between Spain and the United States in 1795. Negotiated with the Spanish government by U.S. Diplomat Thomas Pinckney, this treaty gave the U.S. free navigation of the Mississippi River and storage rights at New Orleans, LA. Resentment towards violation of this treaty in part led to the Louisiana Purchase 8 years later.
8. Ozark region
   The Ozarks are a region of “highlands” that extend southwest to northeast from Oklahoma, through Missouri, and into Illinois. Named after a phonetic translation from the French abbreviation “aux arcs,” for “to Arkansas,” the ozark region contains the highest point in Missouri, Taum Sauk Mountain. It also contains other mountains, rocky hills and valleys, and rivers.
9. James Monroe
   Before serving as President of the United States, James Monroe worked under Thomas Jefferson as one of the diplomats who negotiated the treaty for the Louisiana Purchase with France. Desperate for money for his war effort, French ruler Napoleon Bonaparte agreed with Monroe's and Robert Livingston's plan to sell the Louisiana Territory to the United States in 1803.
10. Osage Plain
    The Osage Plain is the part of the Great Plains of the United States contained in Missouri. Encompassing a triangular portion of western Missouri, the land is for the most part flat (much flatter than the Ozark region to its south). The area is suitable for grazing livestock, as it supports the growing of grass and hay.