The Des Moines River is a tributary of the Mississippi River in the upper Midwestern United States that is approximately 525 miles (845 km) long from its farther headwaters. The largest river flowing across the state of Iowa, it rises in southern Minnesota and flows across Iowa from northwest to southeast, passing from the glaciated plains into the unglaciated hills near the capital city of Des Moines, named after the river, in the center of the state. The river continues to flow in a southeastern direction away from Des Moines, later flowing directly into the Mississippi River.

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.