The critically endangered Mangshan pit viper (Protobothrops mangshanensis), endemic to China’s fragmented Nanling Mountain Range, serves as a model to investigate universal drivers of speciation and population collapse in isolated taxa. Using whole-genome resequencing (23 P. mangshanensis; 41 sympatric relatives), we address how historical biogeography, adaptive divergence, and anthropogenic pressures jointly threaten small populations. Results reveal alarmingly low genetic diversity (θπ = 0.009), 91.92% homozygous SNPs, and negligible gene flow—hallmarks of prolonged isolation and inbreeding. Demographic analyses (PSMC/SMC++) trace population declines to post-Pleistocene habitat fragmentation (~10,000 years ago), a bottleneck shared by mountain-endemic vertebrates globally. Selective sweeps identified 192 genes under adaptation, including DLX5/DLX6 (skeletal growth), Hars (movement suppression), and SPAG6 (reproductive isolation), which collectively drove ecological divergence: increased body size to deter predators, reduced mobility to conserve energy, and reproductive isolation halting hybridization. These genomic signatures reflect a classic speciation trajectory—geographic isolation followed by adaptive and reproductive divergence—common in montane taxa. Critically, the study links extinction risks to synergistic pressures: historical climate shifts fragmenting habitats, contemporary anthropogenic barriers limiting gene flow, and genomic erosion eroding adaptive potential. By integrating paleodemography, climate modeling, and adaptive genomics, we establish a framework applicable to conservation of other fragmented species. Our findings underscore that small populations facing habitat loss and climate change are vulnerable to parallel extinction cascades unless adaptive loci are prioritized in management. This work highlights how genomic tools can disentangle universal speciation mechanisms and extinction drivers, offering actionable strategies for biodiversity preservation in the Anthropocene.