A sample of central Argentina (Córdoba) was genotyped for the first hypervariable region (HVS-I) plus a set of coding region mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) (N = 102) and compared with a data set of Y-chromosome short tandem repeats (Y-STRs; N = 100) previously genotyped in the same individuals. We additionally compiled a database containing more than 4,000, 6,800, and 12,000 HVS-I sequences of Native American, sub-Saharan African, and European origin, respectively. The Y-Chromosome Haplotype Reference Database (YHRD) was used as a reference for the Y-STR profiles from Córdoba. The Native American component is highly prevalent on the maternal side (approximately 41%) in contrast to the Y-chromosome paternal contribution (approximately 2%), indicating a strong gender bias in the colonization and admixture processes that occurred in the recent history of Argentina, in agreement with historical records. The demographic input of African slaves in Córdoba was very high in the eighteenth century (approximately 40% of the total population) but decreased dramatically after a few decades; therefore, the minor traces of sub-Saharan Y-chromosome and mtDNA lineages observed in our sample fit well with these historical records. The European Y-chromosome component of Córdoba (approximately 97%; in contrast to the 57% observed in the mtDNA side) also mirrors the substantial immigration experienced by Argentina during the beginning of the last century, predominantly from Italy and Spain.