High-Speed Rail (HSR) promotes regional development and economic connectivity, yet its impacts remain empirically contested. Using a Geographically and Temporally Weighted Regression (GTWR) model with multidimensional indicators, this study analyzes HSR’s spatiotemporally heterogeneous effects across Chinese regions, city scales, and urban agglomerations. Results show stronger benefits in central and western regions—demonstrating a “catch-up effect”—and limited marginal gains in the developed east. Large cities respond more to connectivity improvements, while smaller cities benefit from enhanced accessibility. Region-specific strategies are recommended, such as increasing network efficiency in less-developed areas and promoting multimodal integration in advanced regions, alongside coordinated industrial planning to support balanced growth.