This study examined the impact of the Head Start Research-based, Developmentally Informed (REDI) preschool intervention on high school outcomes and explored longitudinal mediation. 356 children (58% White, 25% Black, 17% Latinx; 54% female, 46% male; M[subscript age] = 4.49 years) were recruited from Head Start classrooms which were randomized to intervention (N = 192) or "usual practice" (N = 164). REDI effects emerged on high school emotional symptoms (teacher ratings, d = 0.41) and behavior problems (composite of teacher, parent, youth ratings, d = 0.27) with the latter benefits mediated by earlier intervention boosts to social-emotional learning, social adjustment, and parent involvement. REDI had no direct impact on GPA or on-time graduation but promoted these outcomes indirectly mediated by earlier intervention effects.