The river flows in a northeasterly direction from its source in the Appalachian Mountains of northwestern New Brunswick to Chaleur Bay. Its meander length is approximately . The Restigouche is fed by several tributaries flowing south from Quebec's Notre Dame Mountains on the western edge of the Gaspé Peninsula (Kedgwick River, Gounamitz River, Patapédia River, and Matapedia River) as well as the Upsalquitch River flowing north from New Brunswick's Chaleur Uplands.