From a developmental perspective, the increase in depressive symptoms among adolescents over the past decade is of great concern due to the risk of long-term mental health problems extending into adulthood. Informed by the Multicultural Social Justice Framework, we examined multi-level, ecological risk and protective factors of depressive symptoms among adolescents. Data were leveraged from the Florida Youth Substance Abuse Survey (N = 9,717) to examine adolescent reported depressive symptoms, individual risk-taking, family factors, school engagement and involvement, community disorganization and safety, and district level factors. We stratified by race to examine differential associations between risk and protective factors and depressive symptoms among Asian, Black, and Latinx youth. Results indicate that individual and family risk and family protection were associated with depressive symptoms. School and community factors were directly related and interacted with individual and family factors, particularly among Black and Latinx youth. Findings imply the need to examine both proximal and systemic factors.