The Gulf of Saint Lawrence is the world's largest estuary. It is the outlet of the Saint Lawrence River into the Atlantic Ocean.

The river flows into the gulf through the Jacques Cartier Strait between the Côte-Nord region of Quebec and Anticosti Island, and the Honguedo Strait between Anticosti Island and the Gaspé Peninsula.

The gulf is bounded on the north by the Labrador Peninsula, to the east by Newfoundland, to the south by Nova Scotia (particularly Cape Breton Island), and to the east by the Gaspé and New Brunswick. It contains Anticosti Island, Prince Edward Island, and the Magdalen Islands.

It drains into the Atlantic through the Straits of Belle Isle, between Newfoundland and Labrador, and Cabot Strait between Newfoundland and Cape Breton Island.

Besides the Saint Lawrence River itself, tributaries of the Gulf of Saint Lawrence include the Miramichi River, the Natashquan River, and the Matapédia River; arms of the Gulf include the Baie des Chaleurs, the Miramichi River estuary, St. George's Bay, and Northumberland Strait.

The first known exchange between Europeans and natives of the Gulf of St. Lawrence occurred in New Brunswick on July 7, 1534.

On May 29, 1914 the Ocean liner Empress of Ireland sank in Gulf taking 1,024 lives with it.