With the sample data from the Yangtze River Delta region, this empirical study analyses the impact of the digital economy on the high-quality urban development, and explores the mediating and moderating effect of industrial synergy development on the relationship between the two by measuring industrial synergy indicators. The results of the study show that the digital economy promotes the high-quality development of cities by improving the level of industrial synergy development, with a greater promotion in central cities than in the peripheral cities. Industrial synergy can promote the high-quality development of the city, in which the promotion of industrial synergy on the high-quality development of the central city is stronger than that of the high-quality development of the peripheral cities. The moderating effect of industrial synergy strengthens the degree of positive impact of the digital economy, which amplifies the role of the digital economy in promoting the process of high-quality development of the city. Accordingly, it is suggested to further promote the construction of digital economy, strengthen the integration of digital economy and industry, promote the synergistic development of industry to help the high-quality development of the Yangtze River Delta region, and accelerate talent cultivation to provide intellectual support for the high-quality urban development.