Background: Hypertension awareness, treatment, and control programs were initiated in the United States during the 1960s and 1970s. Whereas blood pressure (BP) control in the population and subsequent reduced hypertension-related disease risks have improved since the implementation of these interventions, it is unclear whether these BP changes can be generalized to diverse and high-risk populations. This report describes the 4-decade change in BP levels for the population in a high disease risk southeastern region of the United States. The objective is to determine the magnitude of the shift in systolic BP (SBP) among Blacks and Whites from the Southeast between 1960 and 2005 with the assessment of the unique population cohorts. Methods: A multicohort study design compared BPs from the CHS (Charleston Heart Study) and ECHS (Evans County Heart Study) in 1960 and the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) 4 decades later. The analyses included participants ≥45 years of age from CHS (n=1323), ECHS (n=1842), and REGARDS (n=6294) with the main outcome of SBP distribution. Results: Among Whites 45 to 54 years of age, the median SBP was 18 mm Hg (95% CI, 16–21 mm Hg) lower in 2005 than 1960. The median shift was a 45 mm Hg (95% CI, 37–51 mm Hg) decline for those ≥75 years of age. The shift was larger for Blacks, with median declines of 38 mm Hg (95% CI, 32–40 mm Hg) at 45 to 54 years of age and 50 mm Hg (95% CI, 33–60 mm Hg) for ages ≥75 years. The 95th percentile of SBP decreased 60 mm Hg for Whites and 70 mm Hg for Blacks. Conclusions: The results of the current analyses of the unique cohorts in the Southeast confirm the improvements in population SBP levels since 1960. This assessment provides new evidence of improvement in SBP, suggesting that strategies and programs implemented to improve hypertension treatment and control have been extraordinarily successful for both Blacks and Whites residing in a high-risk region of the United States. Severe BP elevations commonly observed in the 1960s have been nearly eliminated, with the current 75th percentile of BP generally less than the 25th percentile of BP in 1960.