Policymakers across the Southern U.S. have directed considerable attention to regional economic development plans, with mixed results. Questions remain over what types of industries, firms, and/or policies can drive long‐range growth. Over the past two decades, researchers have started to focus on high‐growth firms (HGFs) due to their potential innovation spillovers and job creation prospects, both of which drive further economic development. Employing databases from the Inc. 500, this study explores the dynamics of HGFs within Southern and comparative contexts. The first goal of this paper is to explore Southern HGF activity in comparison with the U.S. at‐large. The second is to examine the geographical characteristics of HGFs within the South, which will include an exploration of locations, industrial mix, and the factors that could encourage HGF development and agglomeration. This paper will also analyze the longer‐term ownership and acquisition patterns of HGFs across the South. Are such firms remaining embedded in the South or moving elsewhere through mergers or acquisitions? The paper concludes with a discussion of the impacts of HGFs on regional economic development and moreover, whether existing policies are conducive to these firms.