Objective We examined the association between retrospective reports of adverse childhood experiences (ACEs) and painful medical conditions. We also examined the mediating and moderating roles of mood and anxiety disorders in the ACEs–painful medical conditions relationship. Method Ten‐year longitudinal data were obtained from the National Comorbidity Surveys (NCS‐1, NCS‐2; N = 5001). The NCS‐1 obtained reports of ACEs, current health conditions, current pain severity, and mood and anxiety disorders. The NCS‐2 assessed for painful medical conditions (e.g., arthritis/rheumatism, chronic back/neck problems, severe headaches, other chronic pain). Results Specific ACEs (e.g., verbal and sexual abuse, parental psychopathology, and early parental loss) were associated with the painful medical conditions. Baseline measures of depression, bipolar disorder, and posttraumatic stress disorder were also associated with the number of painful medical conditions. Anxiety and mood disorders were found to partially mediate the ACEs–painful medical conditions relationship. We determined through mediation analyses that ACEs were linked to an increase in anxiety and mood disorders, which, in turn, were associated with an increase in the number of painful medical conditions. We determined through moderation analyses that ACEs had an effect on increasing the painful medical conditions at both high and low levels of anxiety and mood disorders; though, surprisingly, the effect was greater among participants at lower levels of mood and anxiety disorders. Conclusion There are pernicious effects of ACEs across mental and physical domains. Dysregulation of the hypothalamic‐pituitary‐adrenal stress response and the theory of reserve capacity are reviewed to integrate our findings of the complex relationships.