[Objective] To identify the main driving factors of soil moisture in the middle reaches of the Yellow River, to analyze the impact of land cover and climate change on soil moisture changes in the middle reaches of the Yellow River, and to provide a theoretical basis for regional ecological environmental protection and high-quality development. [Methods] The SiB2 model was used to simulate the surface soil moisture (SSM) and root zone soil moisture (RZSM) in the middle reaches of the Yellow River for the years 2000, 2005, 2010, 2015 and 2020, and to analyze their spatial and temporal distribution patterns; the main driving factors were analyzed by combining the GeoDetector, Random Forest, and SHAP; and the contribution of land cover and climate change to the changes of SSM and RZSM was analyzed by using scenario-setting method. [Results] (1) The SiB2 model can better simulate the soil moisture in the middle reaches of the Yellow River after the parameter calibration. (2) Soil moisture in the middle reaches of the Yellow River showed overall spatial distribution characteristics of high in the south and low in the north, and there were differences in the distribution characteristics of SSM and RZSM under different ecological zones, different seasons and different land cover types. (3) Precipitation, soil type and downward shortwave radiation are the main drivers of SSM in the middle reaches of the Yellow River, and precipitation, soil type and land cover type are the main drivers of RZSM in the middle reaches of the Yellow River, and there are differences in the drivers of soil moisture in different ecological zones. (4) The effect of land cover type conversion on RZSM in the middle reaches of the Yellow River is regionally different, and the main direction of change is the decrease of RZSM due to the increase of LAI. (5) Compared to 2000, the decline in SSM and RZSM in 2020 is dominated by differences in climate change and land cover change, respectively. [Conclusion] Land cover changes in the middle reaches of the Yellow River from 2000 to 2020 led to a decline in soil moisture in the root zone, and precipitation magnitude had an important effect on changes in soil moisture after land cover type conversion.