Most North American trauma systems have designated trauma centres (TCs) including level I (ultraspecialized high-volume metropolitan centres), level II (specialized medium-volume urban centres), and/or level III (semirural or rural centres). Trauma system configuration varies across provinces and it is unclear how these differences influence patient distributions and outcomes. We aimed to compare patient case mix, case volumes, and risk-adjusted outcomes of adults with major trauma admitted to designated level I, II, and III TCs across Canadian trauma systems. In a national historical cohort study, we extracted data from Canadian provincial trauma registries on major trauma patients treated between 2013 and 2018 in all designated level I, II, or III TCs in British Columbia, Alberta, Quebec, and Nova Scotia; level I and II TCs in New Brunswick; and four TCs in Ontario. We used multilevel generalized linear models to compare mortality and intensive care unit (ICU) admission and competitive risk models for hospital and ICU length of stay (LOS). Ontario could not be included in outcome comparisons because there were no population-based data from this province. The study sample comprised 50,959 patients. Patient distributions in level I and II TCs were similar across provinces but we observed significant differences in case mix and volumes for level III TCs. There was low variation in risk-adjusted mortality and LOS across provinces and TCs but interprovincial and intercentre variation in risk-adjusted ICU admission was high. Our results suggest that differences in the functional role of TCs according to their designation level across provinces leads to significant variations in the distribution of patients, case volumes, resource use, and clinical outcomes. These results highlight opportunities to improve Canadian trauma care and underline the need for standardized population-based injury data to support national quality improvement efforts.