Pathogens often have negative effects on wildlife populations, and disease management strategies are important for mitigating opportunities for pathogen transmission. Bovine tuberculosis (Mycobacterium bovis; BTB) is widespread among African buffalo (Syncerus caffer) populations in southern Africa, and strategies for managing this disease vary. In two high profile parks, Kruger National Park (KNP) and Hluhluwe-iMfolozi Park (HIP), BTB is either not actively managed (KNP) or managed using a test-and-cull program (HIP). Exploiting this variation in management tactics, we investigated potential evolutionary consequences of BTB and BTB management on buffalo by examining genetic diversity at IFNG, a locus which codes for interferon gamma, a signaling molecule vital in the immune response to BTB. Both heterozygosity and allelic richness were significantly and positively correlated with chromosomal distance from IFNG in KNP, suggesting that directional selection is acting on IFNG among buffalo in this park. While we did not see the same reduction in genetic variation around IFNG in HIP, we found evidence of a recent bottleneck, which might have eroded this signature due to genome-wide reductions in diversity. In KNP, alleles at IFNG were in significant gametic disequilibrium at both short and long chromosomal distances, but no statistically significant gametic disequilibrium was associated with IFNG in HIP. When, we compared genetic diversity between culled and non-culled subsets of HIP animals, we also found that individuals in the culled group had more rare alleles than those in the non-culled group, and that these rare alleles occurred at higher frequency. The observed excess of rare alleles in culled buffalo and the patterns of gametic disequilibrium in HIP suggest that management may be eroding immunogenetic diversity, disrupting haplotype associations in this population. Taken together, our results suggest that both infectious diseases and disease management strategies can influence host genetic diversity with important evolutionary consequences.