With increasing uncertainty and ambiguity in the external business environment, the risks and challenges faced by enterprises also increase accordingly; resilience has become a necessary characteristic for the evolution and upgrading of enterprise innovation systems, and improving enterprise innovation resilience becomes the key for enterprises to establish sustainable competitive advantages and achieve sustainable development. Based on the panel data of Chinese listed companies and cities, we employ the common factor method to measure enterprise innovation resilience and explore the impact of transportation infrastructure construction on enterprise innovation resilience. The results reveal that, firstly, enterprise innovation resilience shows an overall upward trend, but there is a certain degree of temporal–spatial and industrial disparity. Secondly, transportation infrastructure construction, represented by HSR opening, can significantly improve enterprise innovation resilience. However, this effect performs the following heterogeneity: (1) Regionally, the promotion effect is more obvious in eastern regions, central cities, and non-central cities within 107 km and 764 km away from the central city. (2) For enterprises, compared to state-owned enterprises and non-high-tech industries, transportation infrastructure construction has a greater effect in non-state-owned enterprises and high-tech industries. (3) The higher the degree of centrality and closeness centrality, the more obvious the promotion effect of transportation infrastructure construction. Finally, mechanism tests show that enterprise resource acquisition and resource allocation abilities are important channels for transportation infrastructure construction, to enhance enterprise innovation resilience.