The Margaree River is a river on Cape Breton Island in Nova Scotia. The northeast branch of the river rises in the Cape Breton Highlands; the Southwest Margaree flows northeast from Lake Ainslie. The two branches join at Margaree Forks and flows north to empty into the Gulf of Saint Lawrence at Margaree Harbour, Nova Scotia. The river is 120 km in length and drains an area of 1,375 km².

The gravel bars of the upper Northeast Margaree provide spawning grounds for Atlantic Salmon; its steep valleys provide habitat for American Marten and the rare Gaspé shrew. The Margaree Valley includes a mix of farms and woodlands.

During the 18th century, Acadians settled along the coast near the mouth of the river; the French name for this river was St. Marguerite. Scottish Highlanders began to settle in the Margaree Valley at the beginning of the 19th century.

The Margaree was designated a Canadian Heritage River in 1998.