Objectives: This study examined the relationship between familism and depressive symptoms across relational contexts in adolescence, and whether maternal warmth and support, and school support moderated the relationship between familism and depressive symptoms. Method: A total of 180 Latino adolescents (53% female) in 7th through 10th grades (average age = 14 years) participated in this cross-sectional study. The adolescents lived in an emerging Latino community in a rural area in the U.S. South. Most of the adolescents were Mexican-origin (78%) and born in the United States (60%), while the vast majority of their parents were foreign born (95%). Results: Overall, familism was associated with fewer adolescent depressive symptoms. School support moderated the relationship between familism and adolescent depressive symptoms such that familism’s protective effect was only evident when adolescents reported low levels of school support. In the context of average to high school support, adolescents reported low depressive symptoms regardless of familism. However, maternal warmth and support failed to moderate the relationship. Conclusions: Familism may be most protective for adolescents not feeling supported at school, suggesting that these values may offset the risk of a risky school environment.