While chronic and acute stress are often associated with negative health, the sense of coherence–revised (SOC‐R) is proposed to facilitate coping with stress and promote health. However, research is lacking on the specific mechanisms. Therefore, the current study aimed to investigate potential mediating and moderating mechanisms of SOC‐R in the relationship between stress and health. Using a cross‐sectional design, standardized questionnaires assessed SOC‐R, acute (perceived) stress, early‐life adversity (ELA; indicator for early‐life chronic stress), mental and physical health, and satisfaction with life. Mediation and moderation analyses were conducted with N = 531 Irish adults (mean age: 59.5 years; 58.4% female). Regarding acute (perceived) stress, results showed that SOC‐R and its Manageability subscale significantly mediated the association between perceived stress and mental health, and satisfaction with life. SOC‐R and its Manageability subscale also significantly moderated the association between perceived stress and mental health. Regarding ELA, the Manageability subscale significantly mediated the association between ELA and mental health, and satisfaction with life; and the Balance subscale significantly mediated the association between ELA and physical health. SOC‐R may provide a useful focus for stress‐related research, with future longitudinal studies needed to examine SOC‐R as a long‐term modulating pathway between stress and health.