This paper examines the explosion of tuberculosis infections among First Nations communities of western Canada during the critical period from Canada's acquisition of the Northwest to the early 1880s. In the early 1870s, the disease was relatively rare among the indigenous population of the plains. Within a few years, the situation changed dramatically. By the early 1880s, TB was widely recognized to be the primary cause of morbidity and mortality among First Nations populations. Rather than direct infection from the burgeoning European population in the region, the explosion of the disease was caused by sudden ecological, economic, and political changes in the west that were primarily the result of the imposition of Canadian hegemony.