General patterns of organization in the major histocompatibility complex (MHC) have been successfully explained by the model of birth-and-death evolution, but understanding why certain MHC genes are maintained together into specific haplotypes remains challenging. The haplotype configurations of the functionally important class II DR region have been described in few primates and display important interspecific variability with respect to the extent of allelic variation, the number of loci and/or combinations of loci present. Understanding the evolutionary mechanisms driving such variation is conditional upon characterizing haplotypes in new species and identifying the selective pressures acting on haplotypes. This study explores the variability of haplotype configurations in the Mhc-DRB region (exon 2) for the first time in wild non-human primates, chacma baboons (Papio ursinus). Paur-DRB haplotypes were characterized through segregation studies and linkage disequilibrium. 23 Paur-DRB sequences and 15 haplotype configurations were identified in 199 animals. The Paur-DRB exon 2 is shown to be subjected to intense positive selection and frequent recombination. An approach recently developed for human vaccine studies was used to classify Paur-DRB sequences into supertypes, based on the physico-chemical properties of amino acids that are positively selected, thus most probably involved in antigen recognition. Sequences grouped into the same supertype (thus presumably sharing antigen-binding affinities) are non-randomly distributed within haplotypes, leading to an increased individual diversity of supertypes. Our results suggest that selection favoring haplotypes with complementary sets of DRB supertypes shapes functionally tuned haplotypes in this natural baboon population.