Regional labor and housing markets are not all created equal. Some are equipped with the assets to resist economic shocks, while others are challenged in ways that lead to structural decline. In a forthcoming paper, we applied the legacy city conceptual framework to the geography of U.S. metropolitan areas, dubbing them legacy regions. In this study, we analyze the impact of the Great Recession on the economic health of various clusters of legacy regions. These regions—defined by their possession of both industrial era assets and post-industrial era challenges—greatly differed in their level of resilience following the close of the recession. We model the impact of legacy regions’ pre-recession industrial structure on their post-recession resilience outcomes, paying special attention to the incidence of what we call ‘path-dependent decline,’ which occurred in regions already experiencing job and/or productivity shrinkage in the years leading up to 2007. Finally, we offer several conclusions regarding structural decline in legacy regions (as opposed to cyclical decline) and the geographic heterogeneity of post-recession regional economic recovery.