This study tested a social-ecological model of adolescent substance use. Multilevel modeling was used to investigate how systems, such as parents, peers, schools, and communities, directly influence and interact together to influence adolescent substance use. Participants included 14,548 (50.3% female) middle school students who were 78.6% White, 5.4% Biracial, 4.8% Asian, 4.8% Black, and 3.6% Hispanic. Participants completed a survey with scales assessing substance use, peer influences, parental influences, and characteristics of their school and community. Hierarchical linear modeling (HLM) was used to consider the variation of parental and peer influences on substance use and how schools and communities relate to both substance use and the relationship between substance use and peer and parental factors. Results indicated that a positive school climate and a positive sense of community were associated with less adolescent substance use and that a positive sense of community moderated the relation between peer and parental influence on adolescent substance use, thereby acting as a protective factor.