[Objective] The coupling coordination relationship and driving factors between new urbanization, economic development, and the ecological water environment in the Huaihe River economic belt were analyzed in order to provide a scientific reference for ecological construction and environmental protection in the region. [Methods] An evaluation index system was established for the Huaihe River economic belt. A coupling model and a panel data model were used to analyze the spatio-temporal evolution characteristics and influencing factors of the coupling coordination degree among the three systems from 2010 to 2020. [Results] ① From 2010 to 2020, the comprehensive levels of new urbanization, economic development, and the ecological water environment in the Huaihe River economic belt showed an upward trend, and the coupling coordination degree of the three systems was at a high level. The level of coupling coordination degree continued to increase, and the change trends of the three systems in the eastern, northern, and central-western regions converged, similar to the overall trend. ② Factors such as opening up to the outside world, economic development, industrial structure, water use efficiency, government, science and technology, population, and education had different degrees of coupling coordination for the entire region and for the three sub-regions. [Conclusion] The Huaihe River economic belt should simultaneously focus on improving the quality of urbanization, promoting high-quality economic development, and protecting the ecological water environment while fully utilizing positive factors, reducing the impact of negative factors, and achieving the high-quality coupling coordination development of the three systems.