PURPOSE OF THE STUDY:: To examine the influence of mastery, physical activity levels, and subsequent trajectories of domains of functional health across the adult life course. DESIGN AND METHODS:: We examined 8-year trajectories of physical functioning (handgrip strength) and functional health (physical [RAND PHC12], psychological [RAND MHC12], and cognitive [processing speed]) in a large Australian sample (n = 7,485 at baseline) of 3 cohorts (20–24, 40–44, and 60–64 years). Within- and between-person indirect effects of physical activity on the relationship between mastery and health were examined using multilevel structural equation models. RESULTS:: Mastery was positively related to within-person change in physical and psychological health for all cohorts, and processing speed for the 60s. Between-person mastery was positively associated with all health domains across all cohorts. Physical activity indirectly influenced the between-person relationships between mastery and handgrip strength, physical health, and psychological health in all cohorts, and between mastery and processing speed for the 60s. IMPLICATIONS:: Psychological resources are important mechanisms for functional health as they may drive adaptive behaviors such as physical activity. The within-person association connecting mastery with physical and psychological health trajectories provides promise for interventions that foster or improve a sense of mastery. The findings contribute to the understanding of complex relationships between personal resources and behaviors that aid in successful aging across the life span.