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Hypertension is a key driver of cardiovascular diseases. However, how stressors contribute to the development of hypertension remains unclear. The objective of this study was to examine prospective associations of adverse childhood experiences (ACEs) and adulthood psychosocial disadvantages (APDs) with incident hypertension. Data were from the Mid-life in the United States (MIDUS) study, a national, population-based, prospective cohort study. ACEs were examined via retrospective reports, and APDs including work stress and social isolation were assessed using survey measures. Incident hypertension was defined based on self-reported physician diagnosis. Baseline data were collected in 1995, with follow-up in 2004–2006 and 2013–2014. Cox proportional hazards regression was applied to assess prospective associations of ACEs and APDs with incident hypertension in 2568 workers free from hypertension at baseline. After adjustment for covariates, baseline APDs were associated with increased incident hypertension (aHR and 95% CI = 1.48 [1.09, 2.01]) during a 20-year follow-up, whereas ACEs showed null associations. Moreover, a moderating effect by ACEs was observed—the effect of APDs on risk of hypertension was stronger when ACEs were present (aHR and 95% CI = 1.83 [1.17, 2.86]). These findings underscore the importance of psychosocial stressors as nontraditional risk factors of cardiometabolic disorders. [ABSTRACT FROM AUTHOR]