This paper— part of a comprehensive project on industry clusters and rural competitiveness— explores the role of industrial specialization and rurality on economic performance for counties in the continental United States. Regression models are estimated that evaluate the impact of industry cluster-specific employment shares on per capita income growth overall, as well as in a sequence of different contextual settings. Overall, the results suggest that economic disparities across U.S. counties will diminish. The results also suggest that economic specialization “per se” is not a guarantee for economic growth. Instead, economic growth very much depends on the type of specialization and the contextual setting, with distinct differences between, for example, the metropolitan sphere, the rural sphere, and the rural-metro interface.