Transport infrastructure connectivity is a spatial basis for economic development and the spillover and feedback effects of transport infrastructure investment (TII) have become an impetus for economic growth (EG). However, existing research does not consider the spatial effects of TII on the gross EG and the multiple effects of TII on EG structures. To explore the spatial relationships and the functional routes between TII and EG, the spatial Durbin model (SDM) was used to empirically analyze the spatial spillover effect of TII on EG from geographical and economic perspectives based on panel data from 2007 to 2019 of 35 members and partners of the Organization for Economic Cooperation and Development (OECD+). On this basis, a structural equation model (SEM) was established to reveal the multiple mediating effects of TII on EG. Results show that (1) the SDM–SEM hybrid method can model the spatial spillover effect and function routes of TII on EG based on theoretical analysis and empirical research; (2) according to empirical analysis of the SDM model, the spatial spillover effect in high-income OECD+ countries shows a positive effect under the economic distance, while that in the upper-middle-income countries has a negative effect; (3) an empirical analysis of the function route model implies that TII in high-income OECD+ countries exerts multiple mediating effects and it mainly affects EG indirectly by means including industrial structure (IS), and the rate of contribution of the key function route FR3 is 67.25%. The following suggestions are proposed: (1) it is necessary to enhance the intensity of effective investment in transport infrastructure, focus on weak links of transport infrastructure, and pay attention to investment in burgeoning fields of the OECD+ countries; (2) differentiated TII strategies are required to be formulated according to development of OECD+ countries with different income levels; (3) it is necessary to give full play to the spatial spillover effect and multiple mediating effects of TII on EG and the TII structure should be optimized, so as to improve the economic benefits of TII.
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