Vegetation net primary productivity (NPP) plays a crucial role in assessing the quality and function of terrestrial ecosystems. The Qilian Mountains (QLM) are an important ecological barrier and water conservation area in northwest China. However, the driving factors of the NPP change in the greening (NPP increased) area and browning (NPP decreased) area of QLM remain unclear. This study analyzes the spatiotemporal dynamics and driving factors of NPP in QLM over the past two decades by utilizing hydrometeorological data and human activity (HA) data. Employing spatial and trend analyses to explore the variation of NPP. Additionally, the gravity model was introduced to track the migration of NPP's gravity center, and the Geodetector model was employed to identify the driving factors and their interactive impacts on NPP change. Finally, the Hurst index was used to predict the persistence of the changing trend. Results reveal a fluctuating increasing NPP trend (2.38 gC m^–2 a^–1) in QLM from 2000 to 2020, with cultivated vegetation and broad-leaved forests showing greater increases. Approximately 75.37% of QLM pixels display increased NPP trends, primarily located in the southeastern regions. The NPP gravity center shifted northwestward by 18.24 km. Spatially, high NPP values cluster concentrated in the southeast, while low values cluster concentrated in the northwest. In the greening area, precipitation, vapor pressure deficit, and evapotranspiration dominate NPP changes, contributing 46.1%, 31.5%, and 25.0%, respectively. In the browning area, soil moisture, HA, and precipitation were the primary factors driving NPP change with contributions of 8.4%, 7.6%, and 6.6%, respectively. The results of the Geodetector model indicated that the explanatory power of a single factor was nonlinearly enhanced when it interacted with other factors. The Hurst index suggests that the NPP change was not persistent, showing clear reverse persistent characteristics, which implies uncertainty of the vegetation change in QLM. These findings reveal nonlinear responses of NPP to climate change and human activities in the context of global warming, providing insights for QLM's ecological protection and sustainable development.