Abstract: The upper reaches of the Yangtze River is an important region supporting China's hinterland economy. At the stage of the synergistic development of high-quality economic development and ecological environmental protection, industrial ecological agglomeration is an important path for industrial transformation. On the basis of the connotation of industrial ecological agglomeration, this paper constructed the industrial ecological agglomeration index system from three dimensions of industrial scale agglomeration, innovative agglomeration, and green agglomeration. Based on the panel data of 33 cities in the upper Yangtze River region from 2009 to 2019, the improved entropy method and geographical detector were used to analyze the spatial difference characteristics and associated driving factors of industrial ecological agglomeration. The spatial econometric model was used to explore the spatial spillover effects. The results showed that: (1) The industrial ecological agglomeration level in the study area increased year by year, with a distribution characteristics of "center-periphery" gradient and decreasing diffusion, and presented a spatial pattern of "high in the northeast region and low in the southwest region". (2) Most of the driving factors in the industrial ecological agglomeration system passed the significance test. The strength of the driving forces from stronger to weaker was in the order of industrial innovation agglomeration factor > industrial scale agglomeration factor > industrial green agglomeration factor. Among them, the strength of the influence of industrial green agglomeration factor was much lower than that of industrial scale and innovation agglomeration factor. (3) The interaction between different driving factors in the industrial ecological agglomeration system showed an enhanced relationship. The interaction results of the two-factor enhanced relationship were more abundant than those of the nonlinear enhanced relationship. (4) There was a spatial spillover effect of industrial ecological agglomeration in the upper reaches of the Yangtze River. The environmental regulation, informatization level, social security level and transportation infrastructure construction were shown to have significant driving effects,  and the industrial structure and social security level demonstrated exogenous interaction effects.