Using data from 2369 A-share listed manufacturing firms from 2007 to 2022, this study empirically examines the impact and mechanism of the opening of high-speed rail (HSR) on the high-quality development (HQD) of firms. The study finds that the opening of HSR significantly contributed to the HQD of firms. The mechanism test found that the opening of HSR can promote the HQD of firms by reducing supply chain dependence, and mainly by reducing downstream customer dependence. Meanwhile, the behavioral tendency of firms to reduce supply chain dependence is more obvious in the scenario of higher environmental uncertainty. Heterogeneity studies show that for non-state-owned firms, high-tech industries, and firms in regions with poor supply chain policy environments and digital policy environments, the opening of the HSR has a more significant effect on the promotion of HQD of firms. Further research finds that firms’ reduction in supply chain dependence is beneficial in promoting firm performance stability and accelerating the efficiency of financial flows along the supply chain, but it is also accompanied by a loss of product flow efficiency.