Anthropogenic activities and the resulting climate change affect the type, structure, and function of ecosystems. Understanding vegetation dynamics related to anthropogenic activities and climate change is critical to address the terrestrial carbon cycle in the context of global warming. The objective of this study is to quantify the effects of human-induced land use and land cover change (LUCC) and LUCC-induced climate change on terrestrial net primary productivity (NPP) in the Yellow River Basin (YRB) during 2000–2020 using Weather Research and Forecasting (WRF) model and Integrated Biosphere Simulator (IBIS) model through different experimental scenarios. Results indicated that LUCC can cause an increase in NPP of 1.2 ± 0.67 gC m−2 yr−1 in YRB. The increased precipitation and decreased temperature due to LUCC showed weak negative effect on annual mean NPP in YRB (−0.2 ± 0.74 gC m−2 yr−1). The coupling of LUCC and LUCC-induced climate change increased annual mean NPP approximately 0.6 ± 0.86 gC m−2 yr−1. The impacts of LUCC and LUCC-induced climate change and their coupling effects on NPP were greatest in spring, increasing NPP by 5.1 ± 0.51, 3.4 ± 0.41, and 6.1 ± 0.79 gC m−2 yr−1, respectively. These findings provide important guidance for the sustainable and adaptive management of terrestrial ecosystems in river basin in the context of global change.