This paper examines the effect of expanding transportation networks on spatial industrial growth across the United States from 1953 to 2016. I use a new methodological approach that applies network theory combined with a historic military map to address the two forms of endogeneity present in expanding transportation networks: route placement and construction timing. I find that Interstate counties experienced significant growth in employment and the number of establishments relative to non-Interstate counties. Growth rates are highest within two decades of receiving an Interstate. Results also reveal positive spillovers occurred in later decades among adjacent counties along the metropolitan periphery.