The Innu came to this area to fish the lakes and rivers and to meet with their priest, camping close to the Hudson's Bay Post where they could trade their furs for supplies.

Around 1957 when the Roman Catholic Church was built on the south side of the river, some Innu started to settle. At that time there was pressure from both the Church and the government to mainstream the Innu into the rest of society. In the early 1960s there were several tents and a few houses on the site of the present day community. Today the approximate 1,200 residents of Sheshatshiu, the majority of whom are Innu, support a school, church, several businesses, a clinic and a youth treatment centre.

With the introduction of the "Out Post Program", and in the tradition of their elders, many residents of Sheshatshiu travel deep into the Labrador wilderness for several months in the spring of each year, to live their traditional lifestyle on the land in harmony with nature. While in the country, they hunt and gather food. The children are provided with an informal educational setting where the elders are able to pass down their traditions and heritage and respect for the land. The Innu have tremendous expertise in "living off the land". This community adapts from wage based to non wage economy when appropriate.

The following are members of the Sheshatshiu Innu First Nation:

Anastasia Qupee - Chief
Sam Nui - Councilor
Etienne Riche Jr. - Councilor
Edmund Benuen - Councilor
Christine Nuna - Councilor
Mary Jane Nui - Councilor
Mary Anne Montague - Councilor