Scientific evaluation of the input-output efficiency of economic activities is of great significance for promoting the balanced development of regional economic construction and ecological civilization. Based on the input-output analysis framework, this paper takes 108 prefecture-level and above cities in the Yangtze River Economic Belt from 2003 to 2018 as the research objects, uses Super-EBM model to measure their economic and ecological efficiency, uses kernel density estimation to analyze their spatial and temporal patterns, and uses the network two-stage model to measure their resource and environmental efficiency. The Dagum Gini coefficient is used to further investigate the regional differences and their sources. Finally, the panel Tobit model is used to empirically analyze the driving differences of influencing factors. The results show that: 1) The economic and ecological efficiency of the Yangtze River Economic Belt both decreased first and then increased, and the efficiency of the lower reaches, the middle reaches and the upper reaches of the Yangtze River Economic Belt decreased significantly. The efficiency distribution has the characteristics of "single peak" and "double peak" alternating changes, and the environmental pressure has different effects on the urban input output efficiency. 2) Resource efficiency and economic efficiency are generally similar, while environmental efficiency shows a trend of "long-term slight decline - short-term sharp rise". The main source of regional differences between resource and environmental efficiency is hypervariable density, followed by inter-regional differences and intra-regional differences. 3) Economic development and the innovation ability of input and output efficiency have a positive effect, industrial structure and opening to the outside world have significant negative effects, financial development and fiscal expenditure efficiency have negative effects on resources, the environmental efficiency is positively to the effect of various factors on the middle and lower reaches of the driving effect of significant heterogeneity. On the basis of the research, the paper puts forward measures to improve the regional input-output efficiency, such as establishing cooperation consensus, promoting green transformation, implementing innovative development, expanding green finance, adjusting government intervention, and regulating the introduction of foreign investment.