Foot and mouth disease (FMD) is an important livestock disease impacting mainly intensive production systems. In southern Africa, the FMD virus is maintained in wildlife and its control is therefore complicated. However, FMD control is an important task to allow countries access to lucrative foreign meat market and veterinary services implement drastic control measures on livestock populations living in the periphery of protected areas, negatively impacting local small-scale livestock producers. This study investigated FMD primary outbreak data in Zimbabwe from 1931 to 2016 to describe the spatio-temporal distribution of FMD outbreaks and their potential drivers. The results suggest that: (i) FMD outbreaks were not randomly distributed in space across Zimbabwe but are clustered in the Southeast Lowveld (SEL); (ii) the proximity of protected areas with African buffalos was potentially responsible for primary FMD outbreaks in cattle; (iii) rainfall per se was not associated with FMD outbreaks, but seasons impacted the temporal occurrence of FMD outbreaks across regions; (iv) the frequency of FMD outbreaks increased during periods of major socio-economic and political crisis. The differences between the spatial clusters and other areas in Zimbabwe presenting similar buffalo/cattle interfaces but with fewer FMD outbreaks can be interpreted in light of the recent better understanding of wildlife/livestock interactions in these areas. The types of wildlife/livestock interfaces are hypothesized to be the key drivers of contacts between wildlife and livestock, triggering a risk of FMD inter-species spillover. The management of wildlife/livestock interfaces is therefore crucial for the control of FMD in southern Africa.