This study examines the spatial spillover effects of transportation infrastructure on regional economic growth, utilizing panel data from 31 provincial-level administrative divisions in China from 2003 to 2022. Using the spatial Durbin model (SDM) and three distinct spatial weight matrices—0–1 adjacency, spatial economic–geographical nested, and GDP-based economic distance matrices—this study comprehensively analyzes the multifaceted impacts of transportation infrastructure. The results show that transportation infrastructure significantly promotes economic growth in both local and neighboring regions across all spatial weight matrices. The total effect is most pronounced in geographically proximate regions, with a coefficient of 7.845 (p < 0.01). Regions with similar economic development levels also show strong collaborative effects, with a coefficient of 2.074 (p < 0.01), although the marginal effect of transportation infrastructure diminishes. Furthermore, adjustments in industrial structure and innovation inputs demonstrate a short-term inhibitory effect on economic growth, highlighting the need for synchronized development of transportation infrastructure alongside industrial and innovation policies. This study incorporates multi-dimensional spatial weight matrices to systematically reveal the direct and indirect impacts of transportation infrastructure on regional economies, providing essential empirical support for regional coordination and infrastructure investment policies. The findings offer valuable insights for infrastructure planning in other regions, particularly in formulating policies that promote cross-regional economic cooperation and optimize resource allocation.