The vegetation ecosystem of the Qinghai–Tibet Plateau in China, considered to be the ＂natural laboratory＂ of climate change in the world, has undergone profound changes under the stress of global change. Herein, we analyzed and discussed the spatial-temporal change patts and the driving mechanisms of net primary productivity (NPP) in the Qinghai–Tibet Plateau from 2000 to 2015 based on the gravity center and correlation coefficient models. Subsequently, we quantitatively distinguished the relative effects of climate change (such as precipitation, temperature and evapotranspiration) and human activities (such as grazing and ecological construction) on the NPP changes using scenario analysis and Miami model based on the MOD17A3 and meteorological data. The average annual NPP in the Qinghai–Tibet Plateau showed a decreasing trend from the southeast to the northwest during 2000–2015. With respect to the inter-annual changes, the average annual NPP exhibited a fluctuating upward trend from 2000 to 2015, with a steep increase observed in 2005 and a high fluctuation observed from 2005 to 2015. In the Qinghai–Tibet Plateau, the regions with the increase in NPP (change rate higher than 10％) were mainly concentrated in the Three-River Source Region, the north Hengduan Mountains, the middle and lower reaches of the Yarlung Zangbo River, and the east parts of the North Tibet Plateau, whereas the regions with the decrease in NPP (change rate lower than –10％) were mainly concentrated in the upper reaches of the Yarlung Zangbo River and the Ali Plateau. The gravity center of NPP in the Qinghai–Tibet Plateau has moved southwestward during 2000–2015, indicating that the increment and growth rate of NPP in the southwest part is greater than those of NPP in the northeast part. Further, a significant correlation was observed between NPP and climate factors in the Qinghai–Tibet Plateau. The regions exhibiting a significant correlation between NPP and precipitation were mainly located in the central and east Qinghai–Tibet Plateau, and the regions exhibiting a significant correlation between NPP and temperature were mainly located in the south and east Qinghai–Tibet Plateau. Furthermore, the relative effects of climate change and human activities on the NPP changes in the Qinghai–Tibet Plateau exhibited significant spatial differences in three types of zones, i.e., the climate change-dominant zone, the human activity-dominant zone, and the climate change and human activity interaction zone. These research results can provide theoretical and methodological supports to reveal the driving mechanisms of the regional ecosystems to the global change in the Qinghai–Tibet Plateau.