The arid and semi-arid regions of Northwest China are important ecological barriers in northern China. Under the dual influence of climate change and human activities, it is of great significance to study the spatiotemporal variation characteristics and key driving factors of net ecosystem productivity （NEP） in this region for regional ecological security and sustainable development. Based on multi-source remote sensing and reanalysis datasets such as meteorology, vegetation, soil and topography, and using improved CASA model, soil respiration model, geographic detector and other methods, this study analyzed the spatiotemporal variation characteristics and main influencing factors of vegetation NEP in arid and semi-arid regions of Northwest China from 2000 to 2022. The main findings show that: （1） The multi-year average NEP of vegetation in the study area was 135.32gCm-2, which showed the overall carbon sink function, and the carbon sink was mainly concentrated from May to September. The carbon source area is mainly concentrated in the piedmont low vegetation cover area and the eastern sandy land, accounting for 29%. （2） In the past 23years, the NEP of vegetation in the study area has been increasing, with a change rate of 3.98gCm-2 a-1. Spatially, the area with an increasing trend accounted for 88.77%, and the decreasing trend was mainly concentrated in the piedmont plain area of the Tianshan Mountains. （3） The leaf area index had the strongest explanatory power on the spatial distribution of vegetation NEP （0.75）, followed by soil moisture （0.42）, and the interaction of different elements showed double factor enhancement or nonlinear enhancement effect on NEP. Leaf area index, precipitation and solar radiation were significantly positively correlated with vegetation NEP. The positive correlation area accounted for 73.79%, 16.28% and 15.10% respectively. The areas with significant positive correlation with precipitation are mainly distributed in the western mountainous areas, Hulun Lake and eastern sandy land. There is a significant positive correlation with solar radiation, and the area is mainly distributed in the eastern sandy land. （4）The contribution of climate change to NEP in the arid and semi-arid regions of Northwest China is greater than 80%, accounting for 59.42%. The contribution rate of human activities to NEP is higher than 60%, accounting for 13.90%, which is concentrated in the piedmont plain area of the Altai Mountains and Tianshan Mountains, and a few are scattered in the eastern sandy land. The results of this study are helpful to understand the response mechanism of vegetation NEP to climate change, and provides a theoretical basis for achieving the goal of “carbon peak and carbon neutrality”.