The Upper Mississippi River is today the portion of the Mississippi River upstream of St. Louis, Missouri, United States, at the confluence of its main tributary, the Missouri River. Historically, it may refer to the area above the Arkansas Post, above the confluence of Ohio River, or above Cape Girardeau.

The Mississippi River is the primary river, and second-longest river, of the largest drainage basin in the United States. From its traditional source of Lake Itasca in northern Minnesota, it flows generally south for 2,340 miles (3,766 km) to the Mississippi River Delta in the Gulf of Mexico. With its many tributaries, the Mississippi's watershed drains all or parts of 32 U.S. states and two Canadian provinces between the Rocky and Appalachian mountains. The main stem is entirely within the United States; the total drainage basin is 1,151,000 sq mi (2,980,000 km2), of which only about one percent is in Canada. The Mississippi ranks as the thirteenth-largest river by discharge in the world. The river either borders or passes through the states of Minnesota, Wisconsin, Iowa, Illinois, Missouri, Kentucky, Tennessee, Arkansas, Mississippi, and Louisiana.