(1) Background: African Americans experience high rates of psychological stress and hypertension, which increases their risk of cardiovascular disease with age. Easy-to-collect psychological and biological stress data are valuable to investigations of this association. Hair cortisol concentration (HCC), as a proxy biomarker of chronic stress exposure, provides such advantages in contrast to collection of multiple daily samples of saliva. Objective: To examine the relationships among HCC, perceived stress, mental well-being, and cardiovascular health (systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP)). (2) Methods: Cross-sectional secondary data (N = 25) were used from a mind-body intervention study in hypertensive African Americans ages 65 and older. Data included HCC, a four-item perceived stress scale, SF-36 mental components summary, and SBP/DBP. SBP + 2 (DBP)/3 was used to calculate MAP. (3) Results: The relationship between mental well-being and perceived stress (r = -0.497, p ≤ 0.01) and mental well-being and DBP (r = -0.458, p = 0.02) were significant. HCC change was not significant. In a regression model, every unit increase in well-being predicted a 0.42 decrease in DBP (β = -0.42, 95% CI (-0.69-0.15)) and a 1.10 unit decrease in MAP (β = -1.10, 95% CI (-1.99-0.20)). (4) Conclusions: This study contributes to the knowledge of physiologic data regarding the relationship between MAP and well-being. Findings from this study may aid in the development of interventions that address mental well-being and cardiovascular health in African American older adults with hypertension.