USAID/Malawi launched the Girls’ Empowerment through Education and Health (ASPIRE) Activity in December 2014, beginning a bold cross-sector investment to improve the achievement of girls in upper primary and secondary school in Malawi. USAID’s investment in ASPIRE recognized that for girls’ to achieve academic success, they must enter and stay in school, be learning and safe while in school, and be healthy and supported by their community at all times. ASPIRE targeted all primary and secondary schools in Malawi’s Balaka, Machinga, and Zomba districts. This included 537 primary and 80 secondary schools. In 2018, ASPIRE reached 361,870 primary learners (185,929 girls) and 38,242 secondary learners (17,674 girls) in these schools. The 617 schools and their catchment communities were the focus for interventions to meet the three ASPIRE objectives: Output 1: Reading skills for girls in upper primary school improved; Output 2: Adoption of positive sexual and healthcare-seeking behaviors among youth ages 10–19 increased; Output 3: Key structural and cultural barriers for girls ages 10–19 decreased.