Aboriginal youth are at disproportionate risk for depression and substance use problems. Increasingly, developmental theories have shifted from focusing on vulnerabilities to protective factors for adolescent depression. In particular, theories emphasizing protective factors are relevant when understanding the mental health of Aboriginal youth. However, it is unclear which factors protect against depressive symptomatology among Aboriginal adolescents to promote optimal development. Using multilevel growth curve modeling, the present study had three main objectives. First, we aimed to model the developmental trajectory of depressive symptoms using a sample of off-reserve Aboriginal youth from a national Canadian dataset (ages 12-23). Second, we sought to examine the relationship between alcohol use behaviors, self-esteem, optimism, and the trajectories of depressive symptoms. Lastly, we investigated whether self-esteem and optimism mediated the relationship between alcohol use and depressive symptoms. Gender differences were also examined within each of the study objectives. A sample of off-reserve Aboriginal youth (N = 283; 48.3% male) was selected from cycles 4-7 of the National Longitudinal Survey of Children and Youth. Heavy drinking was a risk factor for depressive symptoms, while self-esteem and optimism were key protective factors for depressive symptoms among early adolescent Aboriginal youth. Further, the developmental trajectory of depressive symptoms among Canadian Aboriginal youth differed for boys and girls once accounting for risk and protective factors. Thus, it is valuable to integrate the protective role of self-esteem and optimism into developmental theories of depression and mental health intervention programs for early adolescent Aboriginal youth.