It is of great significance to carefully evaluate the actual impact of macro-policy formulation on promoting micro-enterprise innovation and implementing innovation-driven strategies. This study utilizes data from Chinese listed companies between 2012 and 2019 and takes the implementation of urban agglomeration policies as a natural experiment. By employing the multi-period differential method, the driving mechanism of urban agglomeration policies on enterprise innovation is investigated. The results show that: (1) Urban agglomeration policies effectively promote the enhancement of regional enterprises’ innovation capability. (2) Urban agglomeration policies reduce enterprise transaction costs through integration effects, mitigate the influence of geographical distance through spillover effects, and stimulate enterprise innovation. (3) Urban agglomeration policies have a regulatory effect on the siphon and spillover mechanism formed by the central city, thereby driving the innovation and development of peripheral micro-enterprises. (4) Further research from the perspectives of enterprises, industries, and locations reveals that the macro, medium, and micro effects of urban agglomeration policies differ, leading to heterogeneity in enterprise innovation responses. Therefore, it is necessary to continue promoting policy planning for urban agglomerations, enhance the coordination of urban policies within urban agglomerations, adjust the influence of the self-mechanism of urban agglomerations, and foster the formation of a multi-center innovation structure and network within urban agglomerations.