Simple SummaryTropical mountains are rather interesting ecosystems that exhibit a diverse array of features of an ecological niche that shapes the geographic distribution of species and their co-occurrence patterns. Both historical and contemporary factors significantly influence species and lineages diversification and distribution on mountains. We studied thePeromyscus mexicanusrodent group, distributed across mountains in Guatemala-Chiapas and Central America. We aimed to describe the phylogeography, demography, current distribution, and potential range changes due to future climate change. Based on a framework of genetic (mitochondrial and nuclear sequences) and ecological niche modeling methods, we show that lineages with particular ecological features and distribution on lowlands and highlands have distinctive demographic histories associated with glacial and interglacial cycles during the Pleistocene–Holocene. Additionally, the distribution range of some lineages will potentially be significantly reduced by future climate change. This information is crucial for management and conservation purposes for these lineages in particular, but also as a cautionary tale for potential climate change impacts on a variety of mountain taxa.AbstractMountains harbor a significant number of the World’s biodiversity, both on tropical and temperate regions. Notably, one crucial gap in conservation is the consideration of historical and contemporary patterns influencing differential distribution in small mammal mountain species and how climate change will affect their distribution and survival. The micePeromyscus mexicanusspecies group is distributed across mountains in Guatemala-Chiapas and Central America, which experienced significant effects of glacial and interglacial cycles. We determined phylogeographic and demographic patterns of lowlands and highlands mountain lineages, revealing that the radiation of modernP. mexicanuslineages occurred during the Pleistocene (ca. 2.6 mya) along Nuclear Central America. In concert with climatic cycles and the distribution of habitats, lowland and highland lineages showed recent population size increase and decrease, respectively. We also estimated the current and future distribution ranges for six lineages, finding marked area size increase for two lineages for which vegetation type and distribution would facilitate migrating towards higher elevations. Contrastingly, three lineages showed range size decrease; their ecological requirements make them highly susceptible to future habitat loss. Our findings are clear evidence of the negative impacts of future climate change, while our ability to manage and conserve these vulnerable ecosystems and mountain species is contingent on our understanding of the implications of climate change on the distribution, ecology, and genetics of wildlife populations.