Based on the panel data of 110 cities in the Yangtze River Economic Belt from 2011 to 2019, a two-way fixed effect model has been applied to study the impact and mechanism of digital economy to urban economic resilience. The empirical results show that the development of digital economy promotes the urban economic resilience of the Yangtze River Economic Belt, which has been supported by robustness and endogenous tests. Urban characteristics can also affect the degree to which digital economy enhances urban economic resilience, whose promotive effect is more significant to cities along the upstream and downstream of the river and with higher levels of industrial synergy and agglomeration. The mediating effect test shows that the digital economy improves urban economic resilience by improving economic efficiency and expanding market size. The moderating effect test indicates that the quality and depth of market synergy agglomeration have a positive moderating effect on the relationship between digital economy and urban economic resilience. Therefore, the government should improve the accuracy of risk warning and the timeliness of risk resistance, optimize resource allocation and expand market scale, and formulate differentiated policies to strengthen urban industrial synergy and agglomeration.