The Ojibwa people used the river to travel between the forests of the interior and Lake Huron. In 1799, the North West Company built a fur trading post at the mouth of the river. This post finally closed in 1900. During the second half of the 19th century, this river was used to transport logs to sawmills at Blind River.
There are several hydroelectric plants on the river.
The lower river is an important spawning ground for lake sturgeon.
The river's name comes from misi-zaagi, which means "river with a wide mouth" in the Ojibwe language.
