Communal livestock farming areas adjoining the Greater Kruger National Park Area within South Africa are part of the Foot-and-mouth disease (FMD) Protection Zone with Vaccination due to the proximity to wildlife reservoirs. FMD and its control affect the productivity of resource-poor farmers who often depend on livestock for their livelihoods. A cross-sectional study was performed with the objectives to evaluate the perceptions of farmers concerning FMD control, estimate the proportion of cattle with presumed protective antibody titres against FMD, as well as the proportion of herds with adequate herd immunity at the wildlife-livestock interface within Mpumalanga Province. One hundred and four farmers were interviewed with 73% (76/104) being cattle owners and the remainder hired cattle herders. The majority of respondents (79%, 82/104) reported a high level of satisfaction with the current animal health programmes in general. The educational level of the respondents varied by satisfaction level: the median (interquartile range; IQR) education level was standard 9 (2–12) for non-satisfied respondents, standard 3 (0–6) for little satisfied and standard 7 (2–11) for very satisfied respondents (P = 0.036). Animals are not always treated at FMD inspections points, but satisfied respondents were more likely to seek veterinary assistance (P = 0.001). The majority of respondents (92%, 96/104) identified the African buffalo (Syncerus caffer) as a risk factor for FMD outbreaks. Liquid-phase blocking ELISA antibody titres ≥1.6log10 were used to indicate positive serology secondary to FMD vaccination. At the time of sampling and relative to this threshold, 23% (95% confidence interval (CI): 12%–34%) of the sampled cattle had positive serology to SAT-1, 41% (95%CI: 33%–48%) to SAT-2 and 29% (95%CI: 19%–39%) to SAT-3. The median (IQR) time between the previous vaccination and sampling was 189 (168–241) days. The sampled cattle had a longer inter-vaccination interval as scheduled by state veterinary services and antibody levels were low at the time of the study. The majority of respondents expressed high satisfaction with the currently applied FMD vaccination programme, which provides an opportunity for progressive adaption of animal health programmes within the study area.