This cluster randomized trial evaluated the effectiveness of a school-based mental health intervention on depressive symptoms among 3,245 adolescents from 42 secondary schools. The intervention included cognitive-behavioral therapy sessions, mental health literacy education, and teacher training. After 12-month follow-up, intervention schools showed significantly greater reduction in depressive symptoms compared to control schools. Subgroup analysis revealed stronger effects for students with baseline depressive symptoms and those from low-income families. School-based mental health programs represent an effective strategy for addressing the growing burden of adolescent depression.