Background: Adverse childhood experiences, depressive symptoms, and functional dependence are interrelated. However, the mechanisms underlying these associations remain unclear. The authors investigated the potential of depressive symptoms to mediate the effect of adverse childhood experiences on functional dependence in older age and whether physical activity moderated this mediation. Method: Data from 25,775 adults aged 62 (9) years from the Survey of Health Ageing and Retirement in Europe were used in adjusted linear mixed-effects models to test whether depressive symptoms mediated the associations between adverse childhood experiences and functional dependence in activities of daily living (ADL) and instrumental ADL (IADL) and whether physical activity moderated these mediations. Results: The results showed a graded association between the number of adverse childhood experiences (0 vs 1 and 0 vs ≥2) and the number of functional limitations in both ADL (bs = 0.040 and 0.067) and IADL (bs = 0.046 and 0.076). These associations were mediated by depressive symptoms. Physical activity reduced the effect of adverse childhood experiences on depressive symptoms (bs = −0.179 and −0.515) and tempered the effect of depressive symptoms on functional dependence both in ADL (b=−0.073) and IADL (b=−0.100). As a result of these reductions, the effect of adverse childhood experiences and depressive symptoms on functional dependence in ADL (Ps > .081) and IADL (Ps > .528) was nonsignificant in physically active participants. Conclusions: These findings suggest that, after age 50, engaging in physical activity more than once a week protects functional independence from the detrimental effects of adverse childhood experiences and depression. In inactive individuals, the detrimental effects of adverse childhood experiences on functional dependence are mediated by depressive symptoms.