The paper discusses the impacts of transportation infrastructure on economic openness within the 27 major cities of Yangtze River Delta of China. Through reviewing relevant literatures, it forms an influencing mechanism and research path based on the theories of New Economic Geography and comparative advantages. In the empirical test, the whole research chooses the panel data from the year 2005 to 2020 to observe the spatial autocorrelation through Global Moran Index (Moran’s I) and Local Moran Scatterplots. Then, the paper builds an econometric function on the basis of Spatial Durbin Model (SDM) to measure the regression results and then decompose the effects. According to the test results, it can be concluded that transportation infrastructure generates positive impacts on economic openness and there truly exists the spatial spillover effect in the Yangtze River Delta. Finally, the paper gives proposals from three aspects which are combined with the policies on integration construction of national strategic deployment of China.