Dynamics of vegetation in arid areas have drawn worldwide attention. The expansion of irrigated cropland (ICE) in arid regions contributes to increased food security and impacts on the extent and development of regional vegetation. However, the quantitative attribution of vegetation growth variation from ICE and biogeochemical factors (e.g., atmospheric CO2 concentration, climatic factors) is still lacking. Here, we assessed key drivers of vegetation growth in the inland arid region of Northwest China (IANC) from 1982 to 2018, including ICE, increased nitrogen rates, elevated atmospheric CO2 concentration (eCO2) and climate drivers, using normalized difference vegetation index (NDVI) and ecosystem gross primary productivity (GPP) as measures. These variables were quantified through trend decomposition, machine learning algorithms, and a satellite-based model. The results show that vegetation growth was increased in IANC mainly due to eCO2 and ICE. After 1995, as the regional climatic aridity intensified, the CO2 fertilization effect on vegetation growth decreased, as the atmospheric CO2 concentration continued to increase. Meanwhile, irrigated cropland area increased sharply, and ICE-driven GPP variation exceeded that driven by eCO2 in the whole region, while the ICE-driven NDVI variation exceeded that due to eCO2 when the ICE reached 6.38%. The ICE effect on regional vegetation growth rather than the CO2 fertilization effect has mitigated the slowdown of the rate of vegetation growth caused by climate changes. Although the ICE is conducive to food security and continuous greening of arid areas, further reclamation will exacerbate water scarcity. Our results provide research base for identifying the scale of sustainable agricultural development.