Although transmission of malaria and other mosquito-borne diseases is geographically heterogeneous, in sub-Saharan Africa risk maps are rarely used to determine which communities receive vector control interventions. We compared outcomes in areas receiving different indoor residual spray (IRS) strategies in Eastern Province, Zambia: (1) concentrating IRS interventions within a geographical area, (2) prioritizing communities to receive IRS based on predicted probabilities of Anopheles funestus, and (3) prioritizing communities to receive IRS based on observed malaria incidence at nearby health centers. Here we show that the use of predicted probabilities of An. funestus to guide IRS implementation saw the largest decrease in malaria incidence at health centers, a 13% reduction (95% confidence interval = 5-21%) compared to concentrating IRS geographically and a 37% reduction (95% confidence interval = 30-44%) compared to targeting IRS based on health facility incidence. These results suggest that vector control programs could produce better outcomes by prioritizing IRS according to malaria-vector risk maps.