The high-speed railway (HSR) plays a crucial role in bolstering regional connectivity and economic and social progress. Nevertheless, there is an ongoing debate around the impact of HSR on the economic and social development of the developing regions. On one hand, developing regions necessitate the implementation of HSR systems to facilitate their progress. On the other hand, they must also mitigate the potential drawbacks and adverse consequences associated. By employing accessibility analysis, urban potential analysis, and geographically-temporal weighted regression modeling, this study aims to comprehensively elucidate the spatially variable impact of HSR on developing regions such as Southwest China. The findings indicate that the implementation of HSR has yielded significant benefits in terms of accessibility, economic growth, and social development in developing regions. However, there is a growing disparity between cities that have HSR connections and those that do not. Additionally, smaller and medium-sized cities situated along the middle section of the HSR route experience relatively less pronounced impacts. This study posits that there is a necessity to enhance the expansion of the HSR network in developing regions, concurrently with the reinforcement of inter-city cooperation and the establishment of urban agglomerations, thereby promoting high-quality and balanced development of the developing regions.