[Objective] The spatio-temporal coupling coordination relationship between high-quality development and water resource conservation and utilization in the urban agglomerations of the middle reaches of the Yellow River in order to provide decision support and a scientific basis for the sustainable use of water resources and effective protection of water ecology in the region. [Methods] Based on the panel data of high-quality development and water resources protection and utilization in 19 cities in the middle reaches of the Yellow River from 2011 to 2021, the coupling coordination degree of high-quality development and water resources protection and utilization and its spatio-temporal characteristics were analyzed by means of combination weighting, coupling coordination degree model and a geographic detector model. [Results] The level of high-quality development and water resource conservation and utilization in the urban agglomeration of the middle reaches of the Yellow River had improved continuously, and regional disparity has gradually narrowed. The coupling coordination degree of the two systems increased over time, with some areas transitioning from the brink of imbalance to the initial stage of coordination. Furthermore, the coupling coordination degree exhibited positive spatial autocorrelation, radiating outward from the two central cities of Xi'an and Zhengzhou City. The degree of dependence on foreign trade and the proportion of tertiary industry output had significant impacts on the coordination of the two systems, with nonlinear enhancement or mutual strengthening relationships among interactive factors. [Conclusion] To enhance the spatial dependence of high-quality development and water resource conservation and utilization in urban agglomerations of the middle reaches of the Yellow River, it will be necessary to strengthen regional cooperation, optimize water resource utilization structures, improve water resource management capabilities, increase investment in science and technology, enhance regional innovation capacity, and actively promote coordinated regional development.