Based on the panel data of its 28 districts and cities, the green and high-quality development level of Huaihe Eco-economic Belt is measured from the three aspects of economy, society and ecology by using the coupling coordination degree model from the synergistic perspective. The spatial characteristics of the green and high-quality development is revealed by using the Moran Index. The research results are as follows: The green and high-quality development level in the districts and cities of Huaihe Eco-economic Belt and the development level of three subsystems of economy, society and ecology have obvious increase trend. From the regional equilibrium, the green and high-quality development levels in three areas of Huaihe River Eco-economic Belt have significant differences, with a decrease trend from the sea-river-lake linkage areas in the east to the Huaihai Economic Zone in the north to the inland rising areas in the middle and west. From the development degree, the development situations of the subsystems of economy and society in various districts and cities are temporally and spatially consistent, but they are significantly different from those of the subsystem of ecology. From the spatial aggregation, the green and high-quality development level in Huaihe River Eco-economic Belt and the subsystem of society have no obvious spatial aggregation, while the subsystems of economy and ecology Zone have significant positive autocorrelation. Accordingly, some policy countermeasures are proposed so as to promote the green and high-quality development in Huaihe River Eco-economic Belt.