According to the National Parks Service, "The Mississippi River watershed is the fourth largest in the world, extending from the Allegheny Mountains in the east to the Rocky Mountains in the west. The watershed includes all or parts of 31 states and 2 Canadian Provinces. The watershed measures approximately 1.2 million square miles, covering about 40% of the lower 48 states.
Communities up and down the river use the Mississippi to obtain freshwater and to discharge their industrial and municipal waste. We don't have good figures on water use for the whole Mississippi River Basin, but we have some clues. A January 2000 study published by the Upper Mississippi River Conservation Committee states that close to 15 million people rely on the Mississippi River or its tributaries in just the upper half of the basin (from Cairo, IL to Minneapolis, MN). A frequently cited figure of 18 million people using the Mississippi River Watershed for water supply comes from a 1982 study by the Upper Mississippi River Basin Committee. The Environmental Protection Agency simply says that more than 50 cities rely on the Mississippi for daily water supply."