Abstract: Harmonious coexistence between humans and nature is a defining feature of Chinese modernization. As a critical strategic region for China’s socio-economic development, the Yangtze River Economic Belt’s human-water system coordination is vital for ecological civilization, high-quality development, and modernization. This study developed a “human-water-land-production-urban” coupling coordination evaluation system, analyzing spatiotemporal patterns and obstacles using the coupling coordination degree model from 2005 to 2020. Results revealed: the human system’s comprehensive level improved steadily, while the water system’s growth slowed during 2010-2015; coupling coordination advanced from mild imbalance to near imbalance, exhibiting a static “high ends, low middle” spatial pattern with provincial capitals leading neighboring cities, and dynamic evolution combining widespread growth with regional disparities. The primary obstacles identified were per capita water resources, the ecological water use ratio, per capita general public budget revenue, and built-up area. The findings offered critical insights for optimizing regional sustainable development.