Recent microsatellite studies of two African buffalo (Syncerus caffer) populations in South Africa indicated a high genetic load due to genome-wide high-frequency occurrence of deleterious alleles. These alleles have a negative effect on two male traits: body condition and bovine tuberculosis resistance. Here, we study the occurrence of these male-deleterious alleles throughout most of the buffalo’s range using previously published microsatellite data (2-17 microsatellite loci genotyped on 1676 animals from 34 localities). We uncovered a continent-wide frequency cline of microsatellite alleles associated with male-deleterious traits, with frequencies decreasing from 25 °S to 5 °N (adjusted R2 = 0.87). Further, there was a continent-wide presence of linkage disequilibrium (LD) between male-deleterious-trait-associated alleles at five linked locus pairs (interlocus distance: 0.5-28 Megabase). The fraction of positive interlocus associations among these locus pairs was 0.65 (95% CI: 0.52-0.77; expected fraction with free recombination: 0.5), indicating that many male-deleterious alleles co-occur in haplotypes. We argue that the allele-frequency cline and LD likely result from genome-wide balancing selection of male-deleterious alleles with equilibrium allele and haplotype frequencies determined by the activity of a sex-chromosomal gene-drive system, the latter which was indicated in earlier studies and seemingly originated in southern Africa. The selection pressures involved must be high to prevent destruction of the allele-frequency cline and haplotypes by LD decay. Since most buffalo populations are stable, our results indicate that natural mammal populations can withstand a high genetic load. Nevertheless, we expect that a high genetic load makes many buffalo populations relatively sensitive to environmental stresses.