Under the background of the new era, the opening of China-European Express (CRE) has an important impact on the commercial circulation agglomeration. Based on the panel data of 284 prefecture-level and above cities in China from 2003 to 2019, this paper empirically investigates the impact and mechanism of the opening of CRE on commercial circulation agglomeration by applying the inter-period DID model. The study shows that, under the conditional of satisfying the parallel trend, the opening of CRE can significantly promote urban commercial circulation agglomeration, which still holds after a series of robustness tests such as placebo test, PSM-DID estimation, and selectivity bias exclusion. The opening of CRE has significantly stronger effect on the commercial circulation agglomeration in cities in the east, with larger population, commercial attraction, non-resource and convenient transportation, and has the greatest impact on the agglomeration of wholesale and retail industries. The commercial circulation agglomeration effect of the opening of CRE has a significant positive spatial hub-and-spoke effect within 150km. The results of the mechanism analysis indicate that the opening of CRE promotes commercial circulation agglomeration by stimulating domestic market potential, improving market accessibility, and enhancing international market gravity.