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OBJECTIVES: The Government of Canada has proposed an 'endgame' target for cigarette smoking that aims to reduce prevalence below 5% by 2035. To meet this difficult goal, it will be necessary to identify populations where interventions will (1) have the greatest impact in reducing the number of smokers and (2) have the greatest impact in addressing smoking disparities. METHOD(S): Using data from the Canadian Community Health Survey, smoking prevalence was estimated for populations that differed with respect to demographic, substance use, and mental health factors. Risk difference, relative risk, and attributable disparity number, which describes the magnitude of the potential impact if the disparity were addressed, were calculated for each group. RESULTS: The strongest disparities (relative risk ⩾ 2) were associated with immigration status (for women), substance use, marital status, and lifetime experience of mental health or substance use disorders. The smallest disparities (relative risk ⩽ 1.5) were associated with sexual orientation, household income, immigration status (men), and province of residence. The groups with the largest attributable disparity number were among those who used cannabis, and those who were not immigrants, not married, and white. CONCLUSIONS: Disparities which were both strong and had a large potential impact on prevalence overall were found for populations facing mental health and substance use concerns. Differences in rankings were found depending on the scale of the measure. Addressing disparities in smoking rates is an important component of developing tobacco endgame strategies.