The Public Health Agency of Canada's integrated bio-behavioural surveillance system-Tracks surveys-assesses the burden of HIV, hepatitis C and associated risks in key populations in Canada. From 2018-2020, Tracks surveys were successfully implemented by First Nations Health Services Organizations in Alberta and Saskatchewan. First Nations-led survey teams invited community members who identified as First Nations, Inuit or Métis to participate in Tracks surveys and testing for HIV, hepatitis C and syphilis. Information was collected on social determinants of health, use of prevention services, substance use, sexual behaviours and care for HIV and hepatitis C. Descriptive statistics are presented. Of the 1,828 survey participants, 97.4% self-identified as First Nations and 91.4% lived in an on-reserve community. Over half (52.2%) were cisgender female, average age was 36.3 years, 82.5% lived in stable housing, 82% had access to primary healthcare and 73.8% reported having good to excellent mental health. Most participants (97%) had a family member who had experienced residential school. High proportions experienced stigma and discrimination (65.6%), financial strain (64.3%) and abuse in childhood (65.1%). Testing for HIV (62.8%) and hepatitis C (55.3%) was relatively high. Prevalence of HIV was 1.6% (of whom 64% knew their infection status). Hepatitis C ribonucleic acid prevalence was 5% (44.9% of whom knew their current infection status). Historical and ongoing experiences of trauma, and higher prevalence of hepatitis C were identified, reaffirming evidence of the ongoing legacies of colonialism, Indian Residential Schools and systemic racism. High participation in sexually transmitted blood-borne infection testing and prevention reflect the importance of First Nations-led culturally sensitive, safe and responsive healthcare services and programs to effect improved outcomes for First Nations peoples.