COVID-19 has seriously affected freight transportation and received increasing attention. However, the effects of the epidemic on transportation modal shift have not been comprehensively explored. Based on the monthly panel data of 21 Chinese provinces from September 2021 to August 2022, the paper adopts a difference-in-differences (DID) model to investigate the epidemic’s impact on the modal shift, including heterogeneity and moderating effects models. We also emphasize the spatial spillover effects and conduct a spatial difference-in-differences (SDID) model. The results indicate that the epidemic has promoted the modal shift from road to waterway but has no long-term promotion. In provinces with well-established waterway infrastructure, higher green levels, and a policy foundation, the epidemic has a more significant improvement in the modal shift. The lower waterway freight rates also can enhance the influence. Moreover, the epidemic has positive spatial spillover effects in neighboring provinces. The decomposition results indicate that the spatial spillover effects are mainly between the province with the epidemic and the neighboring provinces without the epidemic. These findings can provide decision-making reference to the transportation sector in promoting the modal shift from road to waterway in the post-epidemic period.