Africa has the highest burden of infectious diseases in the world and yet the least capacity for its risk management. It has therefore become increasingly important to search for ‘fit-for- purpose’ approaches to infectious disease surveillance and thereby targeted disease control. The fact that the majority of human infectious diseases are originally of animal origin means we have to consider One Health (OH) approaches which require inter-sectoral collaboration for custom-made infectious disease surveillance in the endemic settings of Africa. A baseline survey was conducted to assess the current status and performance of human and animal health surveillance systems and subsequently a strategy towards OH surveillance system was developed. The strategy focused on assessing the combination of participatory epidemiological approaches and the deployment of mobile technologies to enhance the effectiveness of disease alerts and surveillance at the point of occurrence, which often lies in remote areas. We selected three study sites, namely the Ngorongoro, Kagera River basin and Zambezi River basin ecosystems. We have piloted and introduced the next-generation Android mobile phones running the EpiCollect application developed by Imperial College to aid geo-spatial and clinical data capture and transmission of this data from the field to the remote Information Technology (IT) servers at the research hubs for storage, analysis, feedback and reporting. We expect that the combination of participatory epidemiology and technology will significantly improve OH disease surveillance in southern Africa.