Lhasa River Basin, which is the political, economic, and cultural core of Tibet, with typical alpine wetland in Qinghai-Tibet Plateau and main cultivated lands of Tibet. As a result of human activities and climate change, the ecological security and ecology health of the region are now in jeopardy. Because net primary productivity (NPP) can be measured as an indicator of ecosystem health and sustainable development, the aims of the present study were to estimate NPP using a light use efficiency model that was based on the time-series MODIS-NDVI data, in order to analyze the spatial pattern and dynamic changes of NPP, determine the correlation of NPP and climate factors, and explore the driving factors and partitions of NPP variations in the Lhasa river basin from 2000 to 2015. The mean annual NPP for the region over this period was 165.614 g C m^-2 a^-1, with obvious spatial heterogeneity. The distribution of NPP was similar to the distribution of vegetation types, and NPP varied by vegetation type. The NPP also decreased in the river basin as a whole, with a mean change of -1.804 g C m^-2 a^-1. Total NPP was significantly correlated with several climate factors, notably temperature and precipitation, and the correlation between NPP and climate factors had obvious regional differences. The NPP of the herbaceous wetland was negatively correlated with temperature, whereas that of the shrubland was positively correlated with precipitation. Furthermore, 20.81% of the basin area experienced changes in NPP as a result of climate factors, whereas changes in the remaining 79.19% were driven by non-climate factors.