Initially, the organization focused on economic issues, particularly in response to the detrimental effects of the Great Depression on coastal First Nations, especially those involved in the fishing industry.

As the organization's influence grew, so too did its mandate, which began to address broader social issues such as education, housing, and the fight against discriminatory policies.

By this time, the Brotherhood had emerged as one of Canada's leading Indigenous organizations, playing a pivotal role in advocating for the rights and welfare of First Nations communities.

[8] He suggested forming a similar inter-tribal organization to those present, though with a focus on the economic issues being faced by First Nations fishermen in the wake of the Great Depression.

[13] The new organization demanded improved working conditions for First Nations fishermen, in addition to better education, hunting, fishing, and trapping rights, and timber harvesting on off-reserve lands.

[15] Policies implemented by the federal government in response to the outbreak of the Second World War, namely conscription and the decision to start imposing income tax on First Nations commercial fishermen, increased the Brotherhood's membership.

[18] In 1947, the Brotherhood sent delegates to Ottawa to participate in a special joint committee of the Senate and House of Commons, which was tasked with re-evaluating the Indian Act.