Sandstorm is a disastrous weather phenomenon that often occurs in arid and semi-arid areas, endangering the ecological environment and affecting people's lives and property safety seriously. Since the 21st century, the sandstorm weather in the Yellow River Basin has ameliorated obviously. However, the causes of the long-term trends in sandstorms during 21st century were still unknown. In this study, fifteen influencing factors from five aspects: ecology, meteorology, hydrology, geography and man-made were selected to comprehensively analyze the driving mechanism of sandstorm activities in the Yellow River Basin since the 21st century, and the effect of each influencing factor on sandstorm weather was quantified. The results indicated that ecological, meteorological and geographical factors had dominant impacts on the spatio-temporal variation of sandstorms during 2000–2021, while hydrological and human factors played little role in the long-term variation of sandstorms. Sandstorms frequently occurred in semi-desert or grassland or non-high vegetation covered areas in spring. Vegetation coverage, precipitation, surface pressure, surface roughness, and soil moisture content were negatively correlated with sandstorms, while wind speed, friction velocity, evaporation, and soil temperature were positively correlated with sandstorms. Precipitation, runoff, evaporation, soil moisture content, soil temperature, and surface temperature indirectly acted on normalized brightness temperature dust index (NBTDI) and sandstorms by changing soil texture. Normalized Vegetation Index (NDVI) had direct negative effects on NBTDI, while wind speed 10 m (WS10m), slope of sub-gridscale orography (SOSGO), and forecast surface roughness (FSR) had direct positive effects on NBTDI. This study comprehensively revealed the dominant factors and their driving mechanism of sandstorm weather in the Yellow River Basin since the 21st century, which had practical application value for the prevention of sandstorms.