We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 1217 Mexicans from the Mexico City Metropolitan Area living in the northern (N = 751), southern (N = 52), eastern (N = 79), western (N = 33), and central (N = 152) Mexico City, and rural communities (N = 150), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes include 11 Native American haplotypes. Admixture estimates revealed that the main genetic components are Native American (63.85 ± 1.55% by ML; 57.19% of Native American haplotypes) and European (28.53 ± 3.13% by ML; 28.40% of European haplotypes), and a less apparent African genetic component (7.61 ± 1.96% by ML; 7.17% of African haplotypes). Copyright © 2019 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.