Few studies have compared knowledge of the specific health risks of cannabis across jurisdictions. This study aimed to examine perceptions of the health risks of cannabis in Canada and US states with and without legal non-medical cannabis. Cross-sectional data were collected from the 2018 and 2019 International Cannabis Policy Study online surveys. Respondents aged 16–65 (n = 72 459) were recruited from Nielsen panels using non-probability methods. Respondents completed questions on nine health effects of cannabis (including two ‘false’ control items). Socio-demographic data were collected. Regression models tested differences in outcomes between jurisdictions and by frequency of cannabis use, adjusting for socio-demographic factors. Across jurisdictions, agreement with statements on the health risks of cannabis was highest for questions on driving after cannabis use (66–80%), use during pregnancy/breastfeeding (61–71%) and addiction (51–62%) and lowest for risk of psychosis and schizophrenia (23–37%). Additionally, 12–18% and 6–7% of respondents agreed with the ‘false’ assertions that cannabis could cure/prevent cancer and cause diabetes, respectively. Health knowledge was highest among Canadian respondents, followed by US states that had legalized non-medical cannabis and lowest in states that had not legalized non-medical cannabis (P < 0.001). Overall, the findings demonstrate a substantial deficit in knowledge of the health risks of cannabis, particularly among frequent consumers.