Abstract: Net primary productivity (NPP) is an important indicator of regional ecological quality and can reflect the growth status of vegetation. We selected the Luanhe River Basin as the study area, and used trend analysis, Hurst index, and residual trend analysis to examine the spatio-temporal distribution of NPP and investigated the effects of climate change, topographic factors, and human activities. This study analyzed NPP based on meteorological data, land use maps, and remote sensing data MOD17A3 from 2000 to 2015 and aimed to provide a basis for the ecological environmental governance of the river basin. The results showed that: 1) The average annual NPP was 455.04 g(C)·m^-2·a^-1, and the inter-annual variability showed overall growth from 2000 to 2015. Of the total basin area, 32.94% had a significant increase in NPP, whereas 6.98% had a significant decrease. The Hurst index analysis indicated that most NPP changes were in the same direction. 2) There were regional NPP differences in the Luanhe River Basin; the multi-year NPP average was lowest in the low hilly area, intermediate in the plain country, and highest in the middle mountain region. The maximum NPP was in Chengde and Lulong Counties in the Beijing-Tianjin-Hebei water conservation ecological function reserve, with characteristically superior natural environmental conditions. 3) The watershed NPP was positively correlated with the annual average precipitation and the annual average temperature, indicating that temperature was the main climatic factor affecting NPP in the Luanhe River Basin. The accumulation of vegetation NPP was affected by the combined effects of temperature and precipitation. Human activities affected the vegetation NPP by changing the land use intensity, ecological construction, and improving the environment, with positive and negative effects on NPP. Among the different terrain areas, the dominant factors affecting vegetation NPP varied. Overall, the prevailing reasons for NPP increases were climatic factors and human activities; only 1.74% of the regional climate and anthropogenic activities contributed to NPP reduction. The driving characteristics were similar in the low hilly area and the middle and high mountain areas. However, in the low-altitude plain areas, climatic factors or human activity alone led to more significant NPP reductions, accounting for 51.63% of the area. Taken together, this study showed that spatial distribution of NPP was determined by climatic and topographic characteristics, and climate change and human activities strongly affected vegetation NPP.