Comprehensive phylogeographic insights require the integration of evidence across diverse taxa, ecosystems, and geographical regions. However, our understanding of the arid biota of the vast Asian drylands remains limited. Accordingly, this study combined phylogeographic analyses with ecological niche modeling to investigate patterns of diversification and demography of the Central Asian racerunner (Eremias vermiculata), a widespread lizard inhabiting arid eastern-Central Asia (AECA). Mitochondrial DNA (mtDNA) sequences were obtained from 876 individuals across 113 localities, while three nuclear genes—CGNL1, MAP1A, and β-fibint7—were sequenced from 204, 170, and 138 individuals, respectively. Analyses identified four distinct mtDNA lineages corresponding to specific geographic subregions within the AECA, reflecting the topographic and ecological heterogeneity of the region. The detection of mito-nuclear discordance indicated the presence of complex evolutionary dynamics. Divergence dating placed the initial lineage splits at approximately 1.18 million years ago, coinciding with major tectonic activity and climatic aridification that likely promoted allopatric divergence. In particular, lineage diversification within the Tarim Basin suggests that recent environmental shifts may have contributed to genetic divergence. Demographic reconstructions revealed signatures of population expansion or range shifts across all lineages during the Last Glacial Maximum, signifying the combined influence of the unique topography and climate dynamics of the AECA on diversification and demographic change. These results highlight the need for fine-scale genomic investigations to clarify the mechanisms underlying mito-nuclear discordance and local adaptation. Such efforts are essential for advancing understanding of how genetic diversity in dryland taxa responds to environmental change, providing insights into the evolutionary adaptability of species in dynamic landscapes.