HLA profiles of German and Uzbek minorities in Kazakhstan were analyzed and were compared with other populations. In total, 107 and 119 HLA alleles were identified in Germans and Uzbeks, respectively.A*02:01(25.49%),B*07:02(9.80%),B*08:01(9.80%),C*07:02(13.46%),DRB1*07:01(21.57%), and DQB1*03:01(25%) were frequent among Germans, whileA*02:01(17.86%),B*07:02(8.33%),C*04:01(15%),DRB1*07:01(13.09%), andDQB1*03:01(20%) were common alleles in Uzbeks.A*03:01 similar to B*07:02 similar to C*07:02 similar to DRB1*15:01 similar to DQB1*06:02(6%) andA*24:02 similar to B*38:01 similar to C*12:03 similar to DRB1*14:01 similar to DQB1*05:03(3.75%) were the most frequent five-locus haplotypes in Germans and Uzbeks, respectively. Germans of Kazakhstan are genetically related to European Russians, Germans and Eastern Europeans, suggesting their European Russia (Volga Region) origin following their 19th century migration to central Asia. Uzbeks, likely indigenous, were genetically close to Eastern Russians, Europeans, and Asians.