Located on the North Shore of St. Lawrence River, the Moisie River takes its source from water bodies of lakes Opocopa and Ménistouc, having an elevation of above sea level. The main tributaries of the Moisie River are Pékans River which begins south of the Mont Wright (Quebec) and Nipissis River (deriving its source in Lake Wacouno). The watershed of the Moisie River is between that of St. Margaret River (west side) and Matamec River (east side).