Since the reform and opening up, the rough development mode has provided a strong impetus for China’s economic leap forward, however, with the economic development, the protection of the ecological environment has become more and more important. In order to achieve high-quality development with maximized benefits and minimized pollution, measuring the value of urban ecoefficiency by constructing an urban eco-efficiency evaluation system in combination with regional realities has become an important indicator of the quality of regional development. In this study, the super-efficiency SBM model with non-desired outputs was used to measure the urban eco-efficiency of 11 provincial-level administrative regions in the Yangtze River Economic Belt from 2012 to 2020, with Shanghai and Guizhou provinces at the top and bottom of the list with 0.901 and 0.160, respectively, and the overall trend of increasing year by year. The results were analyzed by the Malmquist index and the Tobit model, and significant differences in eco-efficiency were found in different regions. In terms of spatial and temporal patterns, the downstream has obvious advantages over the middle and upstream, with 0.562, 0.302, and 0.229, respectively, showing obvious spatial clustering effects. From the perspective of influencing factors, scientific and technological investment is the core growth point of urban eco-efficiency in the Yangtze River Delta region, and the influence of GDP per capita on urban eco-efficiency passes the significance test of 1%, which has a significant impact; meanwhile, the improvement of industrial structure and the level of urbanization can effectively improve the level of urban eco-efficiency. These findings are of great significance in promoting high-quality regional development. On the one hand, we must strike a balance between development and ecosystems while reducing pollution from agriculture, industry, and households. On the other hand, we must accelerate the transformation and upgrading of traditional industries and strengthen the development of industrial automation while focusing on the green, environmental, and sustainable development of cities. Finally, we must follow the development concept of ecological priority and vigorously research and develop technology to improve the output efficiency of natural resources, labor resources, and capital.