The processes influencing the magnitude of West Nile virus (WNV) transmission from 1 year to the next require thorough investigation. The intensity of WNV transmission is related to the dynamics and interactions between the pathogen, vector, vertebrate hosts, and environment. Climatic variability is one process that can influence interannual disease transmission. South Africa has a long WNV and Sindbis virus (SINV) record where consistent climate and disease relationships can be identified. We relate climate conditions to historic mosquito infection rates. Next, we detect similar associations with reported human outbreaks dating back to 1941. Both concurrent summer precipitation and the change in summer precipitation from the previous to the current summer were strongly associated with WNV and SINV transmission and recorded human outbreaks. Each 100 mm interannual summer precipitation change increased WNV infection rates by 0.39 WNV-positive Culex univittatus/1000 tested Cx. univittatus. An improved understanding of biotic and abiotic disease transmission dynamics may help anticipate and mitigate future outbreaks.