Native Americans long lived along the Mississippi River and its tributaries. Most were hunter-gatherers, but some, such as the Mound Builders, formed prolific agricultural societies. The arrival of Europeans in the 16th century changed the native way of life as first explorers, then settlers, ventured into the basin in increasing numbers. The river served first as a barrier, forming borders for New Spain, New France, and the early United States, and then as a vital transportation artery and communications link. In the 19th century, during the height of the ideology of manifest destiny, the Mississippi and several western tributaries, most notably the Missouri, formed pathways for the western expansion of the United States.
Formed from thick layers of the river's silt deposits, the Mississippi embayment is one of the most fertile agricultural regions of the country, which resulted in the river's storied steamboat era. During the American Civil War, the Mississippi's capture by Union forces marked a turning point towards victory due to the river's importance as a route of trade and travel, not least to the Confederacy. Because of substantial growth of cities and the larger ships and barges that supplanted riverboats, the first decades of the 20th century saw the construction of massive engineering works such as levees, locks and dams, often built in combination.
Since modern development of the basin began, the Mississippi has also seen its share of pollution and environmental problems – most notably large volumes of agricultural runoff, which has led to the Gulf of Mexico dead zone off the Delta. In recent years, the river has shown a steady shift towards the Atchafalaya River channel in the Delta; a course change would be an economic disaster for the port city of New Orleans.
The word Mississippi itself comes from Messipi, the French rendering of the Anishinaabe (Ojibwe or Algonquin) name for the river, Misi-ziibi (Great River).
In the 18th century, the river was the primary western boundary of the young United States, and since the country's expansion westward, the Mississippi River has been widely considered a convenient if approximate dividing line between the Eastern, Southern, and Midwestern United States, and the Western United States. This is exemplified by the Gateway Arch in St. Louis and the phrase "Trans-Mississippi" as used in the name of the Trans-Mississippi Exposition.