<p>Climate change and human activities since the late Pleistocene have profoundly impacted endemic species on the Qinghai-Tibetan Plateau. The Tibetan antelope (<i>Pantholops hodgsonii</i>), a keystone ungulate once heavily poached, experienced unclear demographic fluctuations in response to these pressures. Using whole-genome resequencing, we analyzed 85 Tibetan antelope individuals across three geographic populations to reconstruct their demographic history. Our findings reveal a climate-driven decline during the Last Glacial Period, with a bottleneck during the Last Glacial Maximum (LGM) and post-LGM recovery, aligning with ecological niche modeling that shows habitat contraction and expansion. We further detected repeated human-induced demographic collapses and recovery dynamics in Tibetan antelopes: (i) Neolithic collapse (around 6–4 thousand years ago) probably due to prehistoric overhunting; (ii) Bronze Age expansion (around 2.4 thousand years ago) possibly due to reduced hunting pressure as humans shifted to agro-pastoralism; (iii) an early 15th century expansion potentially from the influence of Tibetan Buddhism on reducing exploitation; (iv) a brief yet severe recent bottleneck during the 1950s–1990s caused by illegal poaching; and (v) a post-bottleneck recovery since 2000 due to enhanced protection. This study clarifies the interplay between climatic and anthropogenic impacts on Tibetan antelopes, offering insights for conserving the biodiversity on the Qinghai-Tibetan Plateau.</p>