Abstract: The contradiction between our country’s rapid economic growth and energy supply and demand restricts urban green development. In consideration of this issue and the fact that economic behavior has spatial interaction, this paper used the data from 2005 to 2017 of 269 cities to construct a dynamic spatial Durbin model and an intermediary effect model to explore the complex mechanism and spatial spillover effect of industrial agglomeration on energy efficiency on the basis of the explanation of the relevant mechanism. The empirical results indicate that industrial agglomeration has a significant spatial spillover effect on energy efficiency in the short term and a significant total effect in the long term. The level of urban innovation has an obvious partial intermediary effect on the relationship between industrial agglomeration and energy efficiency. In addition, further examination shows that the energy policy will affect the local industrial agglomeration mode, and has a greater impact on energy efficiency in the short term; on the condition of the heterogeneity of urban scale and economic development stratification, the spatial spillover effect of industrial agglomeration on energy efficiency is significant. Therefore, it is necessary to fully stimulate the short-term spatial spillover effect of industrial agglomeration, further improve the level of urban innovation and specially pay attention to the development of small and medium-sized cities, so as to promote energy efficiency better.