Yinchuan City, Xi’an City, and Dongying City were selected as typical areas in the upper, middle, and lower reaches of the Yellow River Basin, respectively. The human-water relationship was deconstructed into five subsystems:water, city, land, human, and production. A comprehensive evaluation index system was constructed, and combined with Tapio decoupling model, LMDI decomposition model, obstacle model, and Liang Kleiman information flow methods, the decoupling situation and driving factors between water resource utilization and economic development in typical areas of the Yellow River Basin were explored. The results indicate that the economic growth in typical areas of the Yellow River Basin has basically decoupled from the growth of water resources, but there are significant differences in the driving factors of total water use in different regions. The water subsystem is the key factor restricting the coordinated development of the Yellow River Basin, especially in terms of water resource management and utilization efficiency, which still needs to be improved. There are significant differences in the contradictions of human-water relationship in different regions. Yinchuan City is highly dependent on the Yellow River water caused by lacks local water resources, and the competition between ecological water security and agricultural water demand is prominent. The agglomeration of population and economy in Xi’an City has exacerbated the problems of water scarcity, overexploitation of groundwater, and ecological water use encroachment. Dongying City is deeply affected by the dual pressure of low matching of water and soil resources and high demand for industrial water, which has a profound impact on local human-water relationship.