This study contributes to ongoing scholarship at the nexus of translational research, education reform, and the developmental and prevention sciences. It reports 2-year experimental impacts of a universal, integrated school-based intervention in social-emotional learning and literacy development on children’s social-emotional, behavioral, and academic functioning. The study employed a school-randomized, experimental design with 1,184 children in 18 elementary schools. Children in the intervention schools showed improvements across several domains: self-reports of hostile attributional bias, aggressive interpersonal negotiation strategies, and depression, and teacher reports of attention skills, and aggressive and socially competent behavior. In addition, there were effects of the intervention on children’s math and reading achievement for those identified by teachers at baseline at highest behavioral risk. These findings are interpreted in light of developmental cascades theory and lend support to the value of universal, integrated interventions in the elementary school period for promoting children’s social-emotional and academic skills.