The Mississippi River is the largest river system in North America and is divided into the Upper Mississippi, the Middle Mississippi, and the Lower Mississippi, with the Upper Mississippi upriver of its confluence with the Missouri River, the Middle Mississippi from there downriver to the Ohio River, and the Lower Mississippi from there downriver to the Gulf of Mexico.  The source of the Upper Mississippi branch is traditionally accepted as Lake Itasca, 1,475 feet (450 m) above sea level in Itasca State Park in Clearwater County, Minnesota.

From its origin at Lake Itasca to St. Louis, Missouri, the waterway's flow is moderated by 43 dams. Fourteen of these dams are located above Minneapolis in the headwaters region and serve multiple purposes, including power generation and recreation. The remaining 29 dams, beginning in downtown Minneapolis, all contain locks and were constructed to improve commercial navigation of the upper river. Taken as a whole these 43 dams significantly shape the geography and influence the ecology of the upper river. Beginning just below Saint Paul, Minnesota, and continuing throughout the upper and lower river, the Mississippi is further controlled by thousands of wing dikes that moderate the river's flow in order to maintain an open navigation channel and prevent the river from eroding its banks.

The head of navigation on the Mississippi is the Coon Rapids Dam in Coon Rapids, Minnesota. Before its construction in 1913, steamboats could occasionally go upstream as far as Saint Cloud, Minnesota, depending on river conditions.

The uppermost lock and dam on the Upper Mississippi River is the Upper St. Anthony Falls Lock and Dam in Minneapolis. Above the dam, the river's elevation is 799 feet (244 m). Below the dam, the river's elevation is 750 feet (230 m). This 49-foot (15 m) drop is the largest of all the Mississippi River locks and dams. The origin of the dramatic drop is a waterfall preserved adjacent to the lock under an apron of concrete. Saint Anthony Falls is the only true waterfall on the entire Mississippi River. The water elevation continues to drop steeply as it passes through the gorge carved by the waterfall.

The Upper Mississippi features various natural and artificial lakes, with its widest point being Lake Winnibigoshish, near Grand Rapids, Minnesota, over 7 miles (11 km) across.

Segments of the Mississippi in Minnesota include Lake Itasca to Cass Lake, Cass Lake to Vermillion River, Vermillion River to Palisade, Palisade to Brainerd, Brainerd to Little Falls, Little Falls to St. Cloud, St. Cloud to Anoka, Anoka to Fort Snelling, Fort Snelling to Hastings and Hastings to Iowa.

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