Preventing macroeconomic risk is significant in promoting high-quality development. The digital economy provides a new perspective for responding to the downside pressure, transforming the dynamics of economic growth, and balancing the Growth-Risk tradeoff. Based on an endogenous growth model and the “Growth at Risk” method, this paper derives the theoretical mechanism of the digital economy, measures the regional economic downside risk of 226 cities from 2011 to 2022, and empirically analyzes the effect of the digital economy on the downside risk. The main conclusions show that the digital economy significantly prevents the regional economic downside risk. Second, by promoting the industrial structure, enhancing the market potential, optimizing the consumption structure, and activating entrepreneurship passion, the development of the digital economy shows indirect effects. Furthermore, in cities that lack locational advantages and have weak economic bases, the risk-prevention effect of the digital economy is not significant, and the moderating effect of digital infrastructure construction reduces the heterogeneity of its spatial distribution. This study is of great significance in studying the uncertainty of macroeconomic growth, developing new quality productive forces, and promoting the economy to realize effective qualitative improvement and reasonable quantitative growth.