Ecological sensitivity refers to the adaptability of an ecosystem to external pressure or interference and the corresponding resilience after devastation, and it is one of effective approaches to identify ecological and environmental problems. According to the regional characteristics and the main ecological problems on the Qinghai-Tibet Plateau (QTP), the ecological sensitivity was comprehensively evaluated in this study, by using a spatial distance index system based on land desertification sensitivity, soil erosion sensitivity, landslide sensitivity, and freeze-thaw erosion sensitivity. Moreover, the spatio-temporal variations of ecological sensitivity and conservation regionalization schemes were discussed through spatial autocorrelation and ecological sensitivity change pattern analysis. The results showed that:(1) the comprehensive ecological sensitivity on the QTP decreased from northwest to southeast, and the extremely and severely sensitive areas were mainly concentrated in the northwest and high mountain regions, while the insensitive areas were mainly distributed in the southeast. (2) From 2000 to 2018, the average value of comprehensive ecological sensitivity index on the QTP increased from 1.49 to 1.51, suggesting that the ecological sensitivity gradually decreased and the environment improved significantly. (3) The ecological sensitivity of the QTP had a significantly positive spatial correlation, and the number of low-low (L-L) aggregation grids fluctuated from 7277 in 2000 to 7357 in 2018, indicating that the ecological conditions of the QTP contained a certain risk of deterioration. (4) Based on the analysis of regionally ecological sensitivity change patterns, the QTP could be divided into five categories:strict protection region, ecological degradation region, potential conservation region, ecological improvement region and integrated development region, and the corresponding conservation regionalization schemes were suggested. These results could provide a reference for ecological protection and sustainable development on the QTP, thus effectively promoting the formulation of conservation and management measures.