In 1836 the Hudson's Bay Company established a trading post at North West River and the traders provided the Innu with European tools.

[8] In 1915 the International Grenfell Association established a hospital in North West River to serve the European settlers and indigenous people of the region.

This hospital was closed in 1983 and residents of Sheshatshiu and North West River now rely on Happy Valley-Goose Bay for medical services.

Lester Burry was elected to the convention and he supported future premier Joey Smallwood and his proposal of confederation with Canada.

In the 1980s and 1990s the community of Sheshatshiu, along with the Innu Nation, protested against NATO low-level tactical training flights which utilized CFB Goose Bay.

[10][11][12][13] In 1997, Queen Elizabeth II visited Sheshatshiu and was presented with a letter by community leaders lamenting colonialization.

Due to a variety of factors, including economic adversity, alcoholism and gas sniffing were both rampant in the community, in some cases affecting children as young as five years old.

[19] As of 2020, according to Innu Nation Grand Chief Gregory Rich, Sheshatshiu and Natuashish have a collective population of about 3,000 with about half of that being youths.