Multimorbidity, defined as the presence of two or more chronic conditions, is increasingly prevalent and is a major contributor to ill health in old age. Physical activity (PA) is a key protective factor for health and individuals with multimorbidity could particularly benefit from engaging in PA. However, direct evidence that PA has greater health benefits in people with multimorbidity is lacking. The objective of the present study was to investigate whether the associations between PA and health were more pronounced in individuals with (vs. without) multimorbidity. We used data from 121,875 adults aged 50 to 96 years (mean age = 67 ± 10 years, 55% women) enrolled in the Survey of Health, Ageing and Retirement in Europe (SHARE). Multimorbidity and PA were self-reported. Health indicators were assessed using tests and validated scales. Variables were measured up to seven times over a 15-year period. Confounder-adjusted linear mixed-effects models were used to investigate the moderating role of multimorbidity on the associations of PA with the levels and trajectories of health indicators across aging. Results showed that multimorbidity was associated with declines in physical, cognitive, and mental health, as well as poorer general health. Conversely, PA was positively associated with these health indicators. We found a significant interaction between multimorbidity and PA, revealing that positive associations between PA and health indicators were strengthened in people with multimorbidity – although this stronger association became less pronounced in advanced age. These findings suggest that the protective role of PA for multiple health indicators is enhanced in individuals with multimorbidity.