Objective: Individual differences in childhood cognitive ability have been neglected in the study of how early life psychosocial factors may buffer the long-term health consequences of social disadvantage. In this study, we drew on rich data from two large British cohorts to test whether high levels of cognitive ability may protect children from experiencing the physical and mental health consequences of early life socioeconomic disadvantage. Method: Participants from the 1970 British Cohort Study (BCS; N = 11,522) were followed from birth to age 42, and those from the 1958 National Child Development Study (NCDS; N = 13,213) were followed from birth to age 50. Childhood social disadvantage was indexed using 6 indicators gauging parental education, occupational prestige, and housing characteristics (i.e., housing tenure and home crowding). Standardized assessments of cognitive ability were completed at ages 10 (BCS) and 11 (NCDS) years. Psychological distress, self-rated health, and all-cause mortality were examined from early adulthood to midlife in both cohorts. Results: Early social disadvantage predicted elevated levels of psychological distress and lower levels of self-rated health in both cohorts and higher mortality risk in the NCDS. Childhood cognitive ability moderated each of these relationships such that the link between early life social disadvantage and poor health in adulthood was markedly stronger at low (−1 SD) compared to high (+1 SD) levels of childhood cognitive ability. Conclusions: This study provides evidence that high childhood cognitive ability is associated with a decrease in the strength of socioeconomic status–driven health inequalities.