Background: Growing up in poverty undermines healthy development, producing disparities in the cognitive and social-emotional skills that support early learning and mental health. Preschool and home-visiting interventions for low-income children have the potential to build early cognitive and social-emotional skills, reducing the disparities in school readiness that perpetuate the cycle of poverty. However, longitudinal research suggests that the gains low-income children make during preschool interventions often fade at school entry and disappear by early elementary school. Methods: In an effort to improve the benefits for low-income children, the REDI program enriched Head Start preschool classrooms (study one) and home visits (study two) with evidence-based programming, documenting positive intervention effects in two randomized trials. In this study, REDI participants were followed longitudinally, to evaluate the sustained impact of the classroom and home-visiting enrichments 3 years later, when children were in second grade. The combined sample included 556 children (55% European American, 25% African American, 19% Latino; 49% male): 288 children received the classroom intervention, 105 children received the classroom intervention plus the home-visiting intervention, and 173 children received usual practice Head Start. Results: The classroom intervention led to sustained benefits in social-emotional skills, improving second grade classroom participation, student-teacher relationships, social competence, and peer relations. The coordinated home-visiting intervention produced additional benefits in child mental health (perceived social competence and peer relations) and cognitive skills (reading skills, academic performance). Significant effects ranged from 25% to 48% of a standard deviation, representing important effects of small to moderate magnitude relative to usual practice Head Start. Conclusions: Preschool classroom and home-visiting programs for low-income children can be improved with the use of evidence-based programming, reducing disparities and promoting complementary benefits that sustain in elementary school.