Abstract: As an important ecological barrier and economic belt in China, the study of land use changes in the Yellow River Basin is of great significance to the ecological construction and high-quality development of the Yellow River Basin. Based on the data of land use, climate, topography and anthropogenic activities from 2000 to 2020, this study analyzed the characteristics of land use spatio-temporal pattern changes in the Yellow River Basin by using the land use transfer matrix, land use dynamics, and spatial analysis methods, and further analyzed the impacts of natural and anthropogenic activities and other factors on the land use changes based on the Optimal Parameter Geodetector (OPGD). The results show that: (1) the land use/cover types in the Yellow River Basin from 2000 to 2020 are dominated by grassland, farmland, forests and shrubs, and these four types account for more than 90% of the total area of the basin. Among the different land use/cover types, forests and construction land show a continuous expansion trend, farmland and bare land continue to decrease, ice, water and wetland have little change as a whole, and mutual transfer between farmland and grassland is the main land use/cover transfer type. (2) Wetland, impervious surface and bare land have the largest change amplitude among different land use/cover in the Yellow River Basin from 2000 to 2020, and grassland has the smallest change amplitude. The overall change magnitude of land use shows a trend of decreasing and then increasing. (3) Among the different influencing factors, climatic and socioeconomic factors determine the distribution pattern of land use/cover in the Yellow River Basin. The results of single-factor and interactive factors showed that GDP, temperature and elevation dominated the spatial distribution of land use/cover in the Yellow River Basin, and the interaction of rainfall and elevation mainly explained the spatial distribution of land use/cover. This study can provide scientific references for land resource management and high quality development in the Yellow River Basin.