Abstract: Harmonious coexistence between humans and nature is a defining feature of Chinese modernization. For the Yangtze River Economic Belt, a critical strategic region for China′s socio-economic development, the coordination of its human-water system is vital for ecological civilization, high-quality development, and modernization. Based on the human-water harmony concept and the systematic framework of "human-water-land-industry-urban", we developed a coupling coordination evaluation system for the Yangtze River Economic Belt. By using a coupling coordination degree model, we analyze spatiotemporal patterns of the coupling coordination levels of the human-water system in the Yangtze River Economic Belt from 2005 to 2020 and indentify the main obstacle factors. Results revealed: ① From 2005 to 2020, the human system′s comprehensive level improved steadily, while the water system showed an upward trend but grew slowly during 2010~2015. ② The coupling coordination of the human-water system advanced from mild imbalance to near imbalance, exhibiting a "high at both ends, low in the middle" spatial pattern with provincial capitals leading neighboring cities in a static spatial perspective, and widespread growth with significant regional disparities in a dynamic spatial perspective. ③ The primary obstacles were identified as per capita water resources, the ecological water use ratio, per capita general public budget revenue, and built-up area. The findings offer critical insights for the high-quality development of Yangtze River Economic Belt and the construction of ecological civilization.