Under the influence of global climate change and human activities, the fragile ecosystem in the Qinghai Tibet Plateau is undergoing profound changes. In this study, fully considering the ecological environment background characteristics (freeze-thaw erosion, salinization, soil water erosion), we introduced the extreme climate events factor (extreme high temperature and low temperature, extreme precipitation) and human disturbance factors to construct the evaluation system of fragile ecosystem in the Tibetan Plateau, and then the temporal and spatial patterns of ecosystem vulnerability changes and its driving factors were analyzed. The results showed that the ecosystem vulnerability of alpine ecological fragile region in Qinghai-Tibet Plateau belonged to the level of moderate vulnerability. The spatial distribution pattern showed an increasing trend from southeast to northwest. During 2000-2013, the ecosystem vulnerability firstly increased and then decreased. There was a significant correlation between the spatial and temporal variation patterns of ecosystem vulnerability and topography, climate (temperature, precipitation), and population density. The research results can provide decision support for the protection and restoration of the fragile ecological environment in Qinghai Tibet plateau.