State and local governments frequently invest in policies aimed at stimulating the growth of new industries, but studies of industrial policy and related economic development initiatives cast doubt on their effectiveness. This article examines the role of state-level industrial policies in contributing to the different economic trajectories of two U.S. metro areas—Pittsburgh, Pennsylvania, and Cleveland, Ohio—as they adapted to the decline of their legacy industries. Comparative case studies show that industrial policies in Pittsburgh, which empowered research universities as local economic leaders, contributed to the transformation of the local economy. In Cleveland, by contrast, state industrial policies invested in making incremental improvements, particularly in legacy sectors. The article concludes that by empowering new local economic actors—such as universities—industrial policies can foment political change that enables structural economic change to follow.