St. Anthony Falls in Minneapolis, Minnesota, is the only natural falls on the Mississippi River. Since almost the beginning of settlement in the area by European descendants, the St. Anthony Falls have been used for waterpower. The first allowed settlers were at Ft. Snelling, where construction began in 1820. A sawmill was operating 1821 and a flour mill in 1823. As soon as the land at the sides of the falls became available it was purchased with the intent of using the waterpower of the falls. First lumber mills covered the falls, cutting lumber floated down the Mississippi. After 1870 flour mills started to dominate the area. From 1880 to 1930 the area was the number one flour producer in the US. In later years, some of the power came from steam, but in 1923 half of the waterpower used was for flour milling. Other industries have also used the waterpower.

The Pillsbury A-Mill is a former flour mill located on the east bank of the Mississippi River in Minneapolis, Minnesota. It was the world's largest flour mill for 40 years. Completed in 1881, it was owned by the Pillsbury Company and operated two of the most powerful direct-drive waterwheels ever built, each capable of generating 1,200 horsepower . In 1901 one of the turbines was replaced with a 2,500 horsepower one. Both the mill and its headrace tunnel are contributing resources to the St. Anthony Falls Historic District, which is on the National Register of Historic Places. The mill is also independently on the NRHP. The mill was named a National Historic Landmark in 1966 and has since been converted into the A-Mill Artist Lofts.