The Mistassini River is a river in central Quebec, Canada, draining into the north-western portion of Lac Saint-Jean. It is 298 kilometres (185 mi) long and has a watershed area of 21,900 square kilometres (8,500 sq mi).[1] Its source is between Eau Froide and De Vau Lakes in the northernmost portion of the Rivière-Mistassini Unorganized Territory, just east of the vast Baie-James Municipality.

Despite its name, Lake Mistassini is not in the drainage basin of the Mistassini River, but is about 80 km (50 mi) west from its source. The Mistassini River is easily confused with its tributary, the Mistassibi River.

The upper portion of the river is characterized by a succession of rapids, waterfalls, and cascades. Only the last 25 kilometres (16 mi), from its mouth to Dolbeau-Mistassini, is navigable. Tributaries of the Mistassini River include the Papillon River, the Rivière des Framboises (Raspberry River), the Rivière aux Rats (Rat River), and the Mistassibi River.[2]