Whether regional integration can promote the urban agglomeration to attract foreign direct investment and expand the opening-up is a question worthy of in-depth discussion. This paper constructs a quasi-natural experiment from the perspective of regional integration expansion in the Yangtze River Delta, using the panel data of 208 cities in China from 2005 to 2017. The main purposes are to examine and analyze the common trends and regional differences regarding the influences of regional integration on FDI in entire cities, incumbent cities, and new cities. Next, the internal mechanisms of expansion on FDI are explored. The results show that the regional integration exerted a significant positive effect on the FDI of the entire Yangtze River Delta. For different regions, the effect of regional integration on FDI in the incumbent cities was higher than that in the new cities. In terms of mechanisms, regional integration could affect FDI through industrial division mechanism and market unification mechanism, yet the role of economic connection mechanism exhibited regional differences. The conclusions of this paper bear important enlightenment for promoting the construction of regional integration in China and the high-quality growth of FDI in the Yangtze River Delta.