Background/Objectives: The Human Leukocyte Antigen (HLA) system is composed of a set of genes that codify glycoproteins presenting antigenic proteins to clonotypic T cell receptors in order to start the immune response. Class I and Class II classical loci exhibit high allelic diversity; some of them (or their specific combinations that form haplotypes) are quasi-specific or highly frequent in certain populations and thus are useful for population genetic studies. In this study, an HLA genetic comparison of Chimila, Wayúu, Wiwa, and Barranquilla Colombian nonrelated healthy individuals was carried out together with other populations from all over the world to trace their genetic origin, obtain a virtual transplantation list, and inform future epidemiology studies. Methods: HLA-A, -B, -DRB1, and -DQB1 alleles were sequenced using the PCR-SSOP–Luminex method to analyze the HLA genetic profile of each individual. The data obtained were subsequently processed with standard software to obtain HLA alleles, haplotype frequencies, and genetic distances compared with data from global populations to generate relatedness dendrograms and carry out a correspondence analysis. Results: The results obtained place the Chimila, Wayúu, and Wiwa populations phylogenetically close to the other North and South Amerindian populations included in this study. Amerindians are genetically separated from the rest of the world’s populations. Chimila, Wayúu, and Wiwa present unique extended HLA haplotypes and specific alleles, such as HLA-B*48 or HLA-A*24:01, shared with Oceanian populations. Conclusions: These genetic results and anthropological data support prehistorical trans-Pacific (bidirectional) contacts that contributed to the settlement of America and also suggest that the effects of ancient European gene flow cannot be discarded.