In the United States, stroke incidence and related mortality have declined in the past half century.1,2 This drop is largely because of better recognition and control of modifiable cardiovascular disease risk factors.3,4 There remain significant racial disparities however, and studies and surveillance programs consistently show higher rates of stroke and stroke-related mortality in native born blacks when compared with non-Hispanic whites (NHW).5–9 Nowhere is this racial disparity more evident than in the stroke belt, an area in the Southeastern United States with disproportionately high rates of stroke.10–12 Although a higher prevalence of cardiovascular disease risk factors, specifically hypertension, diabetes mellitus, obesity, and cigarette smoking, account for much of the excess stroke risk, it remains unclear why these cardiovascular comorbidities, and other lifestyle-related risk factors, cluster in this region of the United States, particularly in blacks.13–15 Multiple explanations have been proposed, but the medical community has yet to offer a fully satisfactory explanation for what is driving stroke mortality in the ≈700 hot spot counties of the stroke belt.16 A clue is that these counties also have higher proportions of black residents and unemployment, as well as lower educational status, median income, and healthcare use.16 While often ignored in the medical literature, a history of slavery, and ongoing social segregation, racial discrimination, and economic inequality, provide a historical precedent for the phenotype of poor cardiovascular health observed in several predominantly black communities. Although many reports depict the racial disparities and skew in stroke risk factors in this region of the United States, a PubMed search using the words slavery, slave, stroke, stroke belt, and cardiovascular disease returned no relevant articles. Our goal is to review the historical evidence and test the strength of association …