Heavy drinking and smoking have been found to be among the leading causes of morbidity and mortality within Indigenous youth in North America. The focus of this study was to examine the relative roles of cultural identity, parent-child communication about the harms of substance use (SU), and perception about peers' opinions on heavy drinking and cigarette smoking among Indigenous youth. Strong Indigenous cultural identity, parent-child communication about SU, and affiliation with peers who do not use and/or who disapprove of substance use were all expected to reduce risk for heavy drinking and smoking. Substance use beliefs were hypothesized to mediate these effects. Youth (N = 117; M_age = 14.07; grades 6-11) from two Indigenous communities in Quebec completed self-reports. Consistent with the hypotheses, strong cultural identity predicted increased negative beliefs about substance use, which predicted reduced drinking and smoking. Similarly, affiliating with peers who did not use alcohol predicted decreased positive beliefs about alcohol use, which predicted reduced drinking. Affiliating with peers who did not smoke cigarettes predicted reduced cigarette smoking. Parental influences were not supported in this model. Intervention strategies may benefit from targeting cultural identity, peer groups, and substance use beliefs among Indigenous youth.