Guided by family systems and ecological theories, this study examined the multi-contextual implications of family, school, and individual domains for adolescents' school success. The first goal of this study was to examine reciprocal influences among family climate, school attachment, and academic self-regulation (ASR) during the middle school years. The second goal was to test the relative impact of each of these domains on adolescents' school adjustment and academic achievement after the transition to high school. We applied a cross-lag structural equation modeling approach to longitudinal data from 979 6th grade students and their families, followed over five measurement occasions, from 6th through 9th grade. Controlling for family income, parent education, and adolescent gender, the results revealed reciprocal relationships between the family climate and school attachment over time; both of these factors were related to increases in ASR over time. In turn, ASR was a robust predictor of academic success, with unique associations with school adjustment and academic achievement. Family climate and school adjustment had modest to marginal associations with school adjustment, and no association with academic achievement. Applications of these findings for family-school interventions are discussed.