Quantitatively identifying the relative contributions of climate change and human activity to net primary productivity (NPP) is critical for understanding vegetation dynamics and maintaining regional carbon balances. This study focuses on the driving mechanisms of NPP changes and proposes a research framework for evaluating the relative impacts of climate change and human activity. Based on the Thornthwaite Memorial and CASA models, this study first determined the relative contributions of climate change and human activity to actual net primary productivity (ANPP) changes in the Hengduan Mountain region, and then analyzed the response of ANPP to major climate factors at the pixel scale. We found that the contribution of human activities (66.11%) to ANPP change was about twice that of climate change (33.89%) in the Hengduan Mountain region. The ANPP in the north and south region was mainly affected by temperature and precipitation respectively, while although implementing ecological restoration projects had been important for improving vegetation conditions across the Hengduan Mountain region, several human activities, such as overgrazing, sloping cropland reclamation, and urban expansion, were the main reasons for ANPP’s decrease, especially in dry-hot valley areas. There was a significant gradient difference between in how climate change and human activities influence the ANPP, human activity impacted ANPP more in high relief areas along the horizontal gradient, while climate change impacts on ANPP first decreased then increased with rising elevation along the vertical gradient. This study provides a theoretical basis and methodological reference for quantitatively evaluating ecosystems.