The Mississippi River is the chief river of the largest drainage system in North America. Flowing entirely in the United States (though its drainage basin reaches into Canada), it rises in northern Minnesota and meanders slowly southwards for 2,530 miles (4,070 km) to the Mississippi River Delta at the Gulf of Mexico. With its many tributaries, the Mississippi's watershed drains all or parts of 31 US states and 2 Canadian provinces between the Rocky and Appalachian Mountains. The Mississippi ranks as the fourth longest and tenth largest river in the world. The river either borders or cuts through the states of Minnesota, Wisconsin, Iowa, Illinois, Missouri, Kentucky, Tennessee, Arkansas, Mississippi, and Louisiana.

Native Americans long lived along the Mississippi and its tributaries. Most were hunter-gatherers or herders, but some, such as the Mound builders, formed prolific agricultural societies. The arrival of Europeans in the 1500s changed the native way of life as first explorers, then settlers, ventured into the basin in increasing numbers. The river served first as barrier – forming borders for New Spain, New France, and the early United States – then as vital transportation artery and communications link. In the 19th century, during the height of Manifest Destiny, the Mississippi and several western tributaries, most notably the Missouri, formed pathways for the western expansion of the United States.