Autochthonous Sudanese cattle breeds, namely Baggara for beef and Butana and Kenana for dairy, are characterized by their adaptive characteristics and high performance in hot and dry agro-ecosystems, are used largely by nomadic and semi-nomadic pastoralists. Here we analyzed the diversity and genetic structure of the BoLA-DRB3 gene, a genetic locus linked to the immune response, for the indigenous cattle of Sudan and in the context of the global cattle repository. Blood samples (n=225) were taken from three indigenous breeds (Baggara; n=113, Butana; n= 60 and Kenana; n=52) distributed across six regions of Sudan. Nucleotide sequences were genotyped using the sequence-based typing method. Sequence electropherograms were analyzed using the Assign SBT software. We describe 53 alleles, including seven new, novel alleles. In the Baggara breed the number of alleles was 46 (40 previously reported and six new ones), 33 in the Kenana breed (28 previously reported and five new ones), and 33 in the Butana breed (28 previously reported and five new ones). Venn analysis of Sudanese breeds with Southeast Asian, European and American cattle showed 115 alleles of which 14 were unique to Sudanese breeds. Three of the alleles exhibited gene frequency of > 0.5%, representing 26% of the 53 alleles detected in the native Sudanese cattle. Observed versus expected heterozygosity was higher than 0.93 in all three breeds analyzed and equilibrium status revealed by Hardy-Weinberg Equilibrium suggests pure genetic drift. Gene frequency distributions of Baggara cattle showed an even distribution ( P = 0.016), consistent with the theoretical proportion expected under balancing selection pressure as opposed to positive or neutral selection. In contrast, Butana and Kenana cattle ( P = 0.225 and P = 0.138, respectively) were more congruent with neutral selection, similar to the results obtained for most of the cattle breeds analyzed so far. Sudanese cattle breeds were located within a narrow cloud in an intermediate position between the Zebu and Taurine breeds and close to other Southeast Asian breeds, in accordance with the composite origin of these native breeds, which is also reinforced by the presence of African and Zebu unique BoLA-DRB3 alleles within these breeds. The results of the Principal Component Analysis were in agreement with the overall clustering pattern observed on the NJ and/or UPGMA trees. These results contribute to our understanding of the genetic diversity and distribution pattern of BoLA-DRB3 gene alleles in Sudanese cattle breeds and provide insight into their uniqueness in their ability to survive arrays of tropical diseases and reproduce well in Sudan's harsh environment.