Abstract: The achievement of harmonious advancement in high-standard ecological conservation and high-quality economic development within the Yangtze River Economic Belt (YREB) is of paramount significance for the comprehensive construction of a modern socialist strong country in China. This study concentrated on the 11 provinces and cities within China’s Yangtze River Economic Belt. A comprehensive index evaluation system was constructed. By employing the coupling coordination measurement model, grey relational model, and Panel Vector Autoregression (PVAR) model, this study measured and analyzed the coupling coordination degree and interactive relationship between the ecological environment and high-quality economic development of the Yangtze River Economic Belt from 2012 to 2022. The results indicated that: (1) the coordinated development level between the ecological environment and high-quality economic development in the YREB had undergone a phased evolution from "moderate maladjustment-basic coordination-moderate coordination," exhibiting an overall spatial differentiation pattern of "lower reaches of the Yangtze River > middle reaches of the Yangtze River > upper reaches of the Yangtze River." (1) By the year 2022, only Shanghai, Zhejiang, and Jiangsu had achieved a moderate coordination, while the remaining provinces and cities were all in a state of basic coordination. (3) The correlation between regional subsystems within the YREB and the coupling coordination degree of the two systems showed a relatively balanced degree of association, with the correlation degree of each subsystem indicator generally exceeding 0.8, indicating a robust interactive relationship. (4) In the early development stage of the YREB, the ecological environment was significantly impacted, but subsequently recovered and stabilized over time. The short-term negative impact of the economy on the ecological environment gradually diminished. Accordingly, it was essential to implement measures such as targeted policies, environmental regulation improvements, and enhanced intra-regional cooperation to further promote the coordinated development of the ecological environment and economy in the YREB, to achieve the sustainability of regional development.