Established in 1743 as a trading post by French Fur Trader Louis Fornel, the community later went on to become a hub for the Hudson's Bay Company and home to a hospital and school serving the needs of coastal Labrador.

[3] Central Labrador has been inhabited by Indigenous societies, such as Innu and the Maritime Archaic people, for over 7,000 years due to its bountiful wildlife.

[4][5] In 1743 French fur trader Louis Fornel was the first European to establish a year-long settlement at the present site of North West River.

French settlers from Quebec moved to the area surrounding North West River to work as voyageurs and coureurs des bois (i.e., trappers).

Trappers living in and around North West River would come to the trading post to exchange furs, such as beaver, mink, marten, seal, fox, and bear, for flour, raisins, canvas tents, axes, guns and other goods.

The newest of the Hudson's Bay trading posts was constructed in 1923 and still remains as museum run and maintained by the Labrador Heritage Society.

The mission took doctors and nurses from the United Kingdom, and a handful of Commonwealth countries, to serve the people of Newfoundland and Labrador.

One of these doctors was Dr. Harry L. Paddon, who in 1915 established a hospital in North West River which would eventually serve the entire coast of Labrador.

On July 15, 1903, Leonidas Hubbard with his two companions departed North West River for his tragic canoe expedition, described in Dillon Wallace's book, Lure of the Labrador Wild.

On June 27, 1905, Mina Benson Hubbard departed North West River to complete her husband's failed mission of 1903, and provided the first detailed map of northern Labrador's interior region.

[12] In August, 1905, North West River was the camp site for a solar eclipse expedition sent by the government of the Dominion of Canada and including members of the British Astronomical Association, whose report[13] states that "the resident population of the place consisted only of the Hudson Bay factor [...] and the two factors in charge of a French fur trading station on the opposite bank of the river, some two or three half-breed trappers, and a small company of Montagnais Indians, temporarily encamped at the station".

In July, 1928, Gino Watkins used North West River as the base for an expedition in which he and Jamie Scott explored the area on foot, by canoe and with dog sledge.

The board members of Sivunivut are elected by residents of North West River and the chairperson (currently Trudy Mesher-Barkman) serves in the Nunatsiavut Assembly.