Jacques Cartier came to the site in 1535 during his second voyage. He found Innu people using it as a base for hunting seal. Later that same century, Basques from Spain conducted whaling expeditions on the river.
Tadoussac was founded in 1600 by François Gravé Du Pont, a merchant, and Pierre de Chauvin de Tonnetuit, a captain of the French Royal Navy, when they acquired a fur trade monopoly from King Henry IV. Gravé and Chauvin built the settlement on the shore at the mouth of the Saguenay River, at its confluence with the St. Lawrence, to profit from its location. But the frontier was harsh and only sixteen of the initial 50 settlers survived the first winter. In 1603, the tabagie or "feast" of Tadoussac reunited Gravé with Samuel de Champlain and with the Montagnais, the Algonquins, and the Etchimins." In 1615, the Mission of L'Exaltation-de-la-Sainte-Croix-de-Tadoussac, named in memory of a cross planted by Jean de Quen, was founded by the Récollet Order. Their missionary brothers sang the first Mass there two years later.
Tadoussac remained the only seaport on the St. Lawrence River for 30 years. Historians believe the St. Lawrence Iroquoians, who inhabited the St. Lawrence valley upriver to the west, were defeated and pushed out by the Mohawk before the early 17th century. By the late 17th and early 18th century, Tadoussac was the center of fur trade between the French and First Nations peoples. Competition over the fur trade increased among the nations. Colonists from the Tadoussac area were involved in whaling from 1632 until at least the end of the century.
In the 19th century, with industrialization reaching other parts of Canada, tourists discovered the appeal of this rural village. Wealthy Québécois built a number of vacation villas. A Victorian hotel was built in 1864; it later was lost to a fire. In the 1940s, it was replaced by the large Hotel Tadoussac.
In 1855, the geographic township of Tadoussac was established. In 1899, it was incorporated as a village municipality. In 1937, the Parish Municipality of Tadoussac was formed, but dissolved in 1949 because it had less than 500 inhabitants.