The Three-River Source Region (TRSR), a region with key importance to the ecological security of China, has undergone climate changes and a shift in human activities driven by a series of ecological restoration projects in recent decades. To reveal the spatiotemporal dynamics of vegetation dynamics and calculate the contributions of driving factors in the TRSR across different periods from 1982 to 2012, net primary productivity (NPP) estimated using the Carnegie–Ames–Stanford approach model was used to assess the status of vegetation. The actual effects of different climatic variation trends on interannual variation in NPP were analyzed. Furthermore, the relationships of NPP with different climate factors and human activities were analyzed quantitatively. Results showed the following: from 1982 to 2012, the average NPP in the study area was 187.37 g cm− 2 yr− 1. The average NPP exhibited a fluctuation but presented a generally increasing trend over the 31-year study period, with an increase rate of 1.31 g cm− 2 yr− 2. During the entire study period, the average contributions of temperature, precipitation, and solar radiation to NPP interannual variation over the entire region were 0.58, 0.73, and 0.09 g cm− 2 yr− 2, respectively. Radiation was the climate factor with the greatest influence on NPP interannual variation. The factor that restricted NPP increase changed from temperature and radiation to precipitation. The average contributions of climate change and human activities to NPP interannual variation were 1.40 g cm− 2 yr− 2 and − 0.08 g cm− 2 yr− 2, respectively. From 1982 to 2000, the general climate conditions were favorable to vegetation recovery, whereas human activities had a weaker negative impact on vegetation growth. From 2001 to 2012, climate conditions began to have a negative impact on vegetation growth, whereas human activities made a favorable impact on vegetation recovery.