Social protection (ie, cash transfers, free schools, parental support) has potential for adolescent HIV prevention. We aimed to identify which social protection interventions are most effective and whether combined social protection has greater effects in South Africa. In this prospective longitudinal study, we interviewed 3516 adolescents aged 10-18 between 2009 and 2012. We sampled all homes with a resident adolescent in randomly selected census areas in 4 urban and rural sites in 2 South African provinces. We measured household receipt of 14 social protection interventions and incidence of HIV-risk behaviors. Using gender-disaggregated multivariate logistic regression and marginal effects analyses, we assessed respective contributions of interventions and potential combination effects. Child-focused grants, free schooling, school feeding, teacher support, and parental monitoring were independently associated with reduced HIV-risk behavior incidence (odds ratio: 0.10-0.69). Strong effects of combination social protection were shown, with cumulative reductions in HIV-risk behaviors. For example, girls' predicted past-year incidence of economically driven sex dropped from 11% with no interventions to 2% among those with a child grant, free school, and good parental monitoring. Similarly, girls' incidence of unprotected/casual sex or multiple partners dropped from 15% with no interventions to 10% with either parental monitoring or school feeding, and to 7% with both interventions. In real world, high-epidemic conditions, "combination social protection," shows strong HIV prevention effects for adolescents and may maximize prevention efforts.