We aimed to compare cancer survival in Ontario First Nations people to that in other Ontarians for five major cancer types: colorectal, lung, cervix, breast and prostate. A list of registered or Status Indians in Ontario was used to create a cohort of over 140,000 Ontario First Nations people. Cancers diagnosed in cohort members between 1968 and 2001 were identified from the Ontario Cancer Registry, with follow-up for death until December 31st, 2007. Flexible parametric modeling of the hazard function was used to compare the survival experience of the cohort to that of other Ontarians. We considered changes in survival from the first half of the time period (1968-1991) to the second half (1992-2001). For other Ontarians, survival had improved over time for every cancer site. For the First Nations cohort, survival improved only for breast and prostate cancers; it either declined or remained unchanged for the other cancers. For cancers diagnosed in 1992 or later, all-cause and cause-specific survival was significantly poorer for First Nations people diagnosed with breast, prostate, cervical, colorectal (male and female) and male lung cancers as compared to their non-First Nations peers. For female lung cancer, First Nations women appeared to have poorer survival; however, the result was not statistically significant. Ontario's First Nations population experiences poorer cancer survival when compared to other Ontarians and strategies to reduce these inequalities must be developed and implemented. What's new? Historically, First Nations peoples of Ontario, Canada, experienced lower cancer incidence and higher cancer mortality rates compared with Ontario's general population. The present study examined survival disparities specifically for five major cancer types (breast, cervix, colorectal, lung, and prostate) between First Nations peoples and other populations in Ontario from 1968 to 2001. Over that time, survival improved for other Ontarians for the five cancers investigated but improved among First Nations peoples for just breast and prostate cancer. Since 1992, however, all-cause and specific-cause survival has been especially poor among First Nations peoples for all five cancer types.