Members of Haplomylomys, a subgenus of Peromyscus, are widely distributed in northwestern Mexico and the southwestern United States; due to its taxonomic complexity, the systematics and biogeography of this group have been widely studied. However, the evolutionary relationships between island taxa within the eremicus group remain poorly understood. Our goals were to assess the evolutionary history of Haplomylomys, and to identify geological and climatic events that might have affected its evolutionary history. Phylogenetic relationships were analyzed using 3 mitochondrial gene fragments (Cytb, COI, and COIII) from 61 individuals collected throughout the geographic range of Haplomylomys. Maximum likelihood and Bayesian phylogenetic analyses identified 2 main clades. The 1st includes P. californicus; the 2nd, all the species within the eremicus group divided into 4 clades. Taken together, our phylogenetic analysis and genetic divergence values suggest several taxonomic changes are needed among insular members of the eremicus group. Molecular dating analysis indicates that the phylogeny of Haplomylomys is possibly correlated with the formation of the Colorado River, the latest embayment of the Gulf of California during the Neogene, the trans-peninsular seaway in the central Vizcaino region, and the Last Glacial Maximum; these events may have had an effect at the species and subspecies level for Haplomylomys taxa.