African buffaloes (Syncerus caffer) are reservoir hosts of Southern African Territories (SAT) foot-and-mouth disease (FMD) virus strains. In South Africa, infected buffaloes are found in the FMD-infected zone comprising the Kruger National Park (KNP) and its adjoining reserves. When these buffaloes stray into livestock areas, they pose a risk of FMD transmission to livestock. We assessed 645 records of stray buffalo events (3124 animals) from the FMD infected zone during 1998–2008 for (i) their temporal distribution, (ii) group size, (iii) age and gender composition, (iv) distance from the infected zone fence and (v) outcome reported for each event. A maximum entropy model was developed to evaluate spatial predictors of stray buffalo events and assess current disease control zones. Out of all buffaloes recorded straying, 38.5% escaped from the FMD infected zone during 2000/2001, following floods that caused extensive damage to wildlife fences. Escape patterns were not apparently influenced by season. The median size of stray groups was a single animal (IQR [1–2]). Adult animals predominated, comprising 90.4% (620/686) of the animals for which age was recorded. Of the 315 events with accurate spatial information, 204 (64.8%) were recorded within 1 km from the FMD infected zone. During late winter/spring (June–October), stray buffaloes were found significantly closer to the FMD infected zone (median = 0.3 km, IQR [0.1–0.6]). Less than 13% (40/315) of stray groups reached the FMD protection zone without vaccination, posing a higher risk of spreading FMD to these more susceptible livestock. Model outputs suggest that distance from the FMD infected zone, urban areas and permanent water sources contributed almost 85% to the spatial probability of stray buffalo events. Areas with a high probability for stray buffalo events were well covered by current disease control zones, although FMD risk mitigation could be improved by expanding the vaccination zone in certain areas.