There is little research on the impact of air cargo networks on regional economic development, which is especially notable considering that Chinese airlines gradually adjusted their networks after the introduction of high-speed rail (HSR). This empirical study aims to fill this research gap. Firstly, we used the Ordinary Least Squares (OLS) method to study the effect of the air cargo network on the regional economy. The results show that, in eastern and central China, the higher the clustering coefficient of the domestic air cargo network, the more significant their promotion effect becomes on the GDP per capita, with cities in eastern China benefitting the most from this effect. However, for super-scale cities, the clustering coefficient of the domestic air cargo network has a significant negative effect on the GDP per capita, which is likely because both the air and HSR passenger services crowd out the development opportunities for air cargo. Secondly, we applied the Difference-in-Difference (DID) method in order to measure the impact on the regional economy caused by air cargo under the impact of HSR. The results show that the aviation network adjusted for the impact of HSR produces heterogeneous effects on cities for different regions and scales, and that the international aviation network has greater impacts on cities than the domestic network. In eastern China, HSR and air cargo (both international and domestic networks) promote economic growth simultaneously; in central China, only domestic air cargo has a positive effect on the regional economy; in western China, neither HSR nor air cargo has an obvious effect on the regional economy. Policy implications—such as encouraging the cooperation of HSR and civil aviation—are discussed, and could help bring the functions of the air cargo network in regional economic development into full play