In May 1673, Jesuit priest Jacques Marquette and French trader Louis Jolliet sailed down the Mississippi River in canoes along the area that would later become the state of Missouri. The earliest recorded use of "Missouri" is found on a map drawn by Marquette after his 1673 journey, naming both a group of Native Americans and a nearby river. However, the French rarely used the word to refer to the land in the region, instead calling it part of the Illinois Country. In 1682, after his successful journey from the Great Lakes to the mouth of the Mississippi River at the Gulf of Mexico, René-Robert Cavelier, Sieur de La Salle claimed the Louisiana Territory for France. During the journey, La Salle built several trading posts in the Illinois Country in an effort to create a trading empire; however, before La Salle could fully implement his plans, he died on a second journey to the region during a mutiny in 1685.
During the late 1680s and 1690s, the French pursued colonization of central North America not only to promote trade, but also to thwart the efforts of England on the continent. In that vein, Pierre Le Moyne d'Iberville and Jean-Baptiste Le Moyne, Sieur de Bienville established Biloxi in 1699 and Mobile in 1701 along the Gulf coast, while Antoine Laumet de La Mothe, sieur de Cadillac established Detroit in 1701 along the Great Lakes. From these outposts departed a variety of fur traders and Jesuit missionaries that enabled France to build strong relationships with indigenous tribes and retain control of the continental interior.
Although both Marquette and La Salle had passed Missouri on their journeys, neither had established bases of operations in what would become the state. Encouraged by the building of Mobile and Biloxi, the first to do so was Pierre Gabriel Marest, a Jesuit priest who in late 1700 established a mission on the west bank of the Mississippi at the mouth of the River Des Peres. Marest established his mission station with a handful of French settlers and a large band of the Kaskaskia people, who fled from the eastern Illinois Country to the station in the hope of receiving French protection from the Iroquois. Marest became involved in learning their language and constructed several cabins, a chapel, and a basic fort at the station. However, bands of Sioux were angry at the encroachment of the Kaskaskia onto Sioux lands at Des Peres; these Sioux forced Marest to move the station south and east in 1703 to a new location in Illinois known as Kaskaskia.
From this time up until the building of the first railways in the Mississippi Basin in the mid-19th century, the Mississippi-Missouri river system waterways were the main means of communication and transportation in the region. The earliest traffic up the Missouri likely occurred in the 1680s by unlicensed fur traders; the first known ascent occurred in 1693, and within a decade, more than a hundred traders were moving along the Mississippi and Missouri. These early traders met two tribes within what would become Missouri: the Missouri and the Osage.
The Missouri were a semi-sedentary people with a major village along the Missouri River in northern Saline County, Missouri; they lived at the village primarily during the spring planting and fall harvesting seasons, while pursued game at other time. The Missouri became an ally of the French, eventually even traveling to Detroit to assist in the defense of the town against a Fox tribe attack. The Osage for their part became a more significant player in the development of Missouri history; they lived along the Osage River in Vernon County, Missouri and near the Missouri village in Saline County. Like the Missouri, the Osage lived in semi-permanent villages, and they also both had acquired horses.
The exposure to French activities brought significant changes to the indigenous peoples of Missouri. Although interactions were generally positive between them, the introduction of diseases, alcohol, and firearms proved detrimental to traditional lifestyles and cultures. The increased dependence on European goods altered cultural patterns of craft production, and an increased emphasis on hunting due to commercialism changed Osage marriage patterns. Younger Osage hunters who had achieved wealth from trade sought to increase their power in Osage society, and they at various times challenged the established political order of tribal elders. Although both the Osage and the Missouri were exposed to European diseases such as smallpox and typhus, the Osage suffered only slightly compared to the Missouri, who were drastically reduced in population.