In recent years, China’s transportation infrastructure has undergone significant changes. High-speed rail, as a new and favored mode of transportation, offers travelers convenience, efficiency, and punctuality, replacing many high-pollution transportation methods. Based on the characteristics of high-speed rail, this paper selects data from 30 provinces spanning from 1999 to 2019. It utilizes the double-difference method to evaluate the impact of high-speed rail opening on economic sustainability. It has been found that the introduction of high-speed rail contributes to economic sustainability during the examination period. The mechanism test also reveals that the opening of high-speed rail promotes green and sustainable development through the industrial agglomeration effect. In addition, the opening of high-speed rail (HSR) has a significant time lag effect and a spatial spillover effect on green sustainable development. The conclusion complements the theoretical framework regarding the impact of high-speed rail on the environment and regional economic sustainability. It also provides guidance for the efficient utilization of high-speed rail, which holds both theoretical and practical importance.