Abstract: The vegetation ecosystem of the Qinghai-Tibet Plateau is very sensitive to climate change. In this study, the spatial-temporal evolution patterns of net primary production (NPP) and its driving mechanisms in the Qinghai-Tibet Plateau from 2000 to 2015 were analyzed and discussed by using the gravity center model and other relative models. Subsequently, the relative effects of climate change and human activity on the process of NPP change were quantitatively distinguished. The results have been listed. (1) From 2000 to 2015, the annual mean NPP in the Qinghai-Tibet Plateau showed a decreasing trend from southeast to northwest. In terms of interannual changes, the annual mean NPP of different subregions showed a fluctuating upward trend. (2) During the past 16 years, the gravity center of NPP in the Qinghai-Tibet Plateau moved southwest indicating that the increment and growth rate of NPP in the southwestern part were greater than those in the northeastern part. (3) The regions with significant correlation between NPP and precipitation were mainly located in the central and southeastern parts of the Qinghai-Tibet Plateau and the middle and lower reaches of the Yarlung Zangbo River Basin. The regions with significant correlation between vegetation NPP and temperature were mainly located in southern Tibet, northern Hengduan Mountains, and central and northern Qinghai-Tibet Plateau. (4) The relative effects of climate change and human activity on the process of NPP change in the Qinghai-Tibet Plateau had significant spatial-temporal differences with a spatial pattern of “four lines-five regions.” The research results can provide theoretical and methodological support to reveal the response mechanism of regional ecosystems to global change in the Qinghai-Tibet Plateau.