Aside from the admixture in between indigenous people and individuals from overseas, populations in Mexico changed significantly after the Spanish conquest of the sixteenth century, forming a complex history that has actually been underutilized in understanding the hereditary population structure of Mexicans. To presume historic procedures of seclusion, dispersal, and assimilation, we took a look at the phylogeography of mitochondrial (mt) DNA and Y-chromosome lineages in 3,026 people from 10 urban and 9 indigenous populations by identifying single nucleotide polymorphisms. A geographical array with a predominance of Amerindian family trees was observed for mtDNA, with northern native populations being divergent from the main and southern indigenous populations; urban populations revealed low differentiation with isolation by range. Y-chromosome variation distinguished urban and native populations through the Amerindian haplogroup Q frequency. The MtDNA and the Y-chromosome together mostly identified city and native populations, with different geographic varieties for both. Gene flow across geographical range and between the metropolitan and indigenous worlds appears to have modified the pre-Hispanic phylogeography in central and southern Mexico, generally by displacement of ladies, while maintaining the native isolation in the north, southeast, and Zapotec regions. The majority of Amerindian mtDNA diversity currently happens in city populations and seems reduced amongst native individuals.