[Objective] This study aims to scientifically recognize and evaluate the equilibrium of domestic, ecological, and production water use in Yangtze River Basin from the perspectives of water and soil spatial matching and differences in per capita water use. [Methods] The Gini coefficient and Lorenz asymmetry coefficient were used to analyze the disequilibrium of water use and its sources. Furthermore, the matching degree index was used to analyze the matching degree between water use, regional area, and population. [Results] The water usage per unit area in Yangtze River Basin was 92.7 mm, and the per capita water use was 1 194.0 L/d. Among these, production water use was the highest, followed by domestic water use, while ecological water replenishment was the lowest. Analysis based on water use per unit area and per capita water use showed that, overall, water use was higher in the eastern region, followed by the central region, and lower in the western region. Based on the administrative divisions, Yangtze River Basin was divided into 18 sub-regions according to provincial administrative boundaries. The Gini coefficients and Lorenz asymmetry coefficients for domestic, ecological, production, and total water use in Yangtze River Basin were calculated from the perspectives of water and soil spatial matching and differences in per capita water use. The Gini coefficients for the spatial distribution of domestic, ecological, production, and total water use in Yangtze River Basin were 0.42, 0.53, 0.51, and 0.49, respectively. The Gini coefficients for per capita water use were 0.10, 0.37, 0.25, and 0.21, respectively. Further analysis using matching degree index to evaluate the matching degree between water use, regional area, and population revealed that the matching degrees for domestic, ecological, production, and total water use with regional area were 0.83, 0.80, 0.81, and 0.81, respectively, and with population were 0.97, 0.90, 0.92, and 0.93, respectively. [Conclusion] Differences in water use are constrained by the inherent endowment of water resources, and the uneven spatial distribution of water resources directly leads to the disequilibrium in water use. The spatial distribution of domestic, ecological, production, and total water use in Yangtze River Basin exhibits disequilibrium, while per capita water use is relatively balanced, with a high degree of matching between water use, regional area, and population. Water resource management must balance “people-oriented” and “spatial equity” principles, coordinating domestic, ecological, and production water use through technological advancements and institutional innovations to reduce disparities in water use per unit area and per capita water use. The research findings can provide important support for the rational utilization of water resources and the realization of human-water harmony.