The Net Primary Productivity (NPP) is an important indicator quantifying ecosystem status, process and undying mechanisms due to global climate change and human activities. The potential NPP (NPP_CL) and actual NPP (NPP_RS) were estimated through GLOPEM-CEVSA model driven by the only interpolated climate data, and both climate and remote sensing data, respectively, for the near 40 years from 1981 to 2018. The human activities dominated NPP (NPP_HA) was defined as the difference between NPP_RS and NPP_CL. The method was applied in the Sanjiangyuan National Park, one of the first national parks in China, to explore the impacts of human activity under global climate change. The results showed that:(1) the average NPP_RS was 309.70 g C m^-2 a^-1, accounting for 61.65% of the NPP_CL for the whole region. For the three sub-parks, the NPP_RS were 249.88 g C m^-2 a^-1, 140.18 g C m^-2 a^-1 and 330.55 g C m^-2 a^-1 in the Yellow River headwater, Yangtze River headwater and Lancang River headwater, respectively. (2) The NPP_RS was increasing significantly by a speed of 2.00 g C m^-2 a^-1, which was faster than the NPP_CL (1.74 g C m^-2 a^-1). The speed ratio of NPP_RS to NPP_CL were 89.13%, 90.23% and 77.43% for the three sub-parks by the above oder, respectively, which meant the Lancang Park was most impacted by human activities. (3) In the terms of climate impact, temperature had a stronger impact on the trend of NPP. Specifically, annual total precipitation, average annual maximum temperature and minimum temperature explained 51% and 73% of the interannual variation of NPP_CL and NPP_RS in the whole region, which can explain 48% and 58%, 52% and 69%, 42% and 50% of the interannual variability in the NPP timeseries in the Yellow River, Yangtze River and Lancang River sub-park, respectively. (4) Human activities had a negative influence over the most areas and became stronger to the southeast from the northwest. And the area showing a negative influence from human activities on the productivity changes decreased from 79.12% before 2000 to 56.34% after 2000. The total NPP over the whore negative area decreased from -71.41 Tg C to -38.72 Tg C, and the human activity as the dominant factor increased from 18.73% to 38.76% for the same two periods. It illustrated that the ecological protection and restoration of the Three-River Headwaters Region have contributed to an increasing vegetation productivity, but the protection and restoration measures should be further implemented.