The Manistique River is a 71.2-mile-long (114.6 km) river in the U.S. state of Michigan that winds southward through the central Upper Peninsula from its headwaters near Lake Superior to its mouth in Lake Michigan. It drains approximately 1,461 square miles (3,780 km2) of the Upper Peninsula, including most of Schoolcraft County and small portions of Alger County, Delta County, Luce County, and Mackinac County.