Rabies is a fatal neurological pathogen that is a persistent problem throughout the developing world where it is spread primarily by domestic dogs. Although the disease has been extensively studied in wildlife populations in Europe and North America, the dynamics of rabies in domestic dog populations has been almost entirely neglected. Here, we demonstrate that rabies epidemics in southern and eastern Africa cycle with a period of 3–6 years and show significant synchrony across the region. The observed period is shorter than predictions based on epidemiological parameters for rabies in domestic dogs. We find evidence that rabies prevention measures, including vaccination, are affected by disease prevalence and show that a simple model with intervention responses can capture observed disease periodicity and host dynamics. We suggest that movement of infectious or latent animals combined with coordinated control responses may be important in coupling populations and generating synchrony at the continental scale. These findings have important implications for rabies prediction and control: large-scale synchrony and the importance of intervention responses suggest that control of canine rabies in Africa will require sustained efforts coordinated across political boundaries.