The fields of water resource utilization efficiency and industrial structure upgrading in the Yellow River Basin are weak, and promoting their spatially coordinated development is of great significance to its high-quality development. Based on the establishment of the indices of water resource utilization efficiency and industrial structure upgrading in the Yellow River Basin, the coupling coordination degree model is used to analyze the coordinated development of water resource utilization efficiency and industrial structure upgrading in 9 provinces and regions of the Yellow River Basin from 2004 to 2018. Then the spatial characteristics of the coordinated development of the two systems are revealed by using the global Moran index. The research shows that the overall utilization efficiency of water resources is stable, and fluctuates with the change of economic cycle in time sequence. The industrial structure upgrading index has a relatively stable growth trend. The two systems both have significant spatial differences. In general, the coordination of the Yellow River Basin has improved from the mild imbalance recession stage in 2004 to the harmoniously coordinated development stage in 2018. From the provincial perspective, the coordination of provinces keeps improving before 2012, and the growth trend slows down after 2012 and some provinces with heavy industrial structure decrease in coordination degree. In terms of spatial agglomeration, the coupling coordination degree before 2010 has obvious weak autocorrelation characteristics, while the autocorrelation is not significant after 2010. Finally, some suggestions are put forward based on the research conclusions and development trends so as to promote the high-quality development of the Yellow River Basin.