Background The initiation of desert conditions in the Tarim Basin in China since the late Miocene has led to the significant genetic structuring of local organisms. Tarim Red Deer (Cervus elaphus yarkandensis, TRD) have adapted to the harsh environmental conditions in this basin, including high solar radiation and temperature, aridity, and poor nutritional conditions. However, the underlying genetic basis of this adaptation is poorly understood. Results We sequenced the whole genomes of 13 TRD individuals, conducted comparative genomic analyses, and estimated demographic fluctuation. The ∂a∂i model estimated that the TRD and Tule elk (Cervus canadensis nannodes) populations diverged approximately 0.98 Mya. Analyses revealed a substantial influence of the Earth’s climate on the effective population size of TRD, associated with glacial advances and retreat, and human activities likely underlie a recent serious decline in population. A marked bottleneck may have profoundly affected the genetic diversity of TRD populations. We detected a set of candidate genes, pathways, and GO categories related to oxidative stress, water reabsorption, immune regulation, energy metabolism, eye protection, heat stress, respiratory system adaptation, prevention of high blood pressure, and DNA damage and repair that may directly or indirectly be involved in the adaptation of TRD to an arid-desert environment. Conclusions Our analyses highlight the role of historical global climates in the population dynamics of TRD. In light of ongoing global warming and the increasing incidence of droughts, our study offers insights into the genomic adaptations of animals, especially TRD, to extreme arid-desert environments and provides a valuable resource for future research on conservation design and biological adaptations to environmental change.