In Malawi, scale up of malaria control measures has not resulted in expected decreases in Plasmodium falciparum prevalence. Interventions are targeted to individuals with the highest disease risk: pregnant women and children under age five. However, most infection is concentrated in school-aged children (SAC, aged five to 15) who are unlikely to access interventions. We hypothesized that the high burden of infection in SAC was related to a high frequency of asymptomatic infections, and prolonged carriage of untreated asymptomatic infections. We aimed to: describe the association between age and asymptomatic P. falciparum infection; assess the impact of asymptomatic infections on subsequent clinical disease; and predict the impact on prevalence of targeting interventions to SAC. A longitudinal cohort study with 120 individuals aged one through 50 years was conducted in a high-prevalence rural area. Using data from cross-sectional studies and the cohort study, a mathematical model was constructed. Incident infections and length of infection persistence did not significantly differ between SAC and children under five. Asymptomatic infections in all ages were unlikely to develop into clinical disease, and were associated with decreased risk of subsequent clinical malaria. Newly acquired infections were associated with increased risk of clinical disease. Modeling predicted that targeting interventions to SAC leads to greater decreases in P. falciparum prevalence in Malawi compared to current intervention strategies. Ensuring both children under five and SAC had equal access to interventions leads to the greatest decreases in prevalence. Biological and behavioral factors may interact to cause the disparity in P. falciparum prevalence observed in cross-sectional data from Malawi. Our data suggests that, for all measures, when participants had equal access to malaria control measures, SAC were similar to children under five. Asymptomatic infections were associated with decreased risk of disease, but did not appear to be protective against clinical disease when new parasites were introduced. Thus, treatment of asymptomatic infections may be a viable strategy to decrease prevalence in Malawi. However, policy needs to address the disparity in access to malaria control interventions, which appears to be driving high P. falciparum prevalence both in SAC and the community.