Dengue outbreaks have persistently occurred in eastern African countries for several decades. We assessed each outbreak to identify risk factors and propose a framework for prevention and impact mitigation. Seven out of ten countries in eastern Africa and three islands in the Indian Ocean have experienced dengue outbreaks between 1823 and 2014. Major risk factors associated with past dengue outbreaks include climate, virus and vector genetics and human practices. Appropriate use of dengue diagnostic tools and their interpretation are necessary for both outbreak investigations and sero-epidemiological studies. Serosurvey findings during inter-epidemic periods have not been adequately utilised to prevent re-occurrence of dengue outbreaks. Local weather variables may be used to predict dengue outbreaks, while entomological surveillance can complement other disease-mitigation efforts during outbreaks and identify risk-prone areas during inter-epidemic periods. The limitations of past dengue outbreak responses and the enormous socio-economic impacts of the disease on human health are highlighted. Its repeated occurrence in East Africa refutes previous observations that susceptibility may depend on race. Alternate hypotheses on heterotypic protection among flaviviruses may not be applied to all ecologies. Prevention and mitigation of severe dengue outbreaks should necessarily consider the diverse factors associated with their occurrence. Implementation of phased dengue mitigation activities can enforce timely and judicious use of scarce resources, promote environmental sanitation, and drive behavioural change, hygienic practices and community-based vector control. Understanding dengue epidemiology and clinical symptoms, as determined by its evolution, are significant to preventing future dengue epidemics. Copyright © 2016 John Wiley & Sons, Ltd.