The main branch of the river rises from wetlands and coldwater tributaries from within Independence, Brandon and Springfield townships in Oakland County.

The main branch flows 83.0 miles (133.6 km)[3] from its headwaters to Lake St. Clair in Harrison Township.

In 1995, the designation was expanded to include the entire watershed of the river and the lower nearshore of Lake St. Clair.

[4] The French explorers of the late 17th century knew the river as the Nottawasippee, an Ojibwe term that means "like rattlesnakes."

This was also the name given to the Huron people by the region's Anishinaabe (Ojibwe, Odawa, and Potawatomi) inhabitants.