We examined the effects of physical activity (PA) and body mass index (BMI) longitudinal patterns (trajectories) on subjective measures of mobility, function, and disability in adults and assessed whether effects of PA trajectories on function varied due to BMI. Group-based trajectory analyses were used to determine patterns of change in PA and BMI using data from the Health and Retirement Study 1931–1941 birth cohort (n = 10,507). Physical function was assessed by Mobility Limitations (0–5 scale) and Large Muscle Function (0–4 scale) Indexes, as well as with score for activities of daily living (ADLs) and instrumental activities of daily living (IADLs), with higher scores being worse. Our analyses estimated four distinct PA trajectories: decreasing, (2) fluctuating, (3) stable high, and (4) emergent (previously low/sedentary with increased PA over the study period). Worse mobility limitations, large muscle function, ADLs, and IADLs were associated with Decreasing and Fluctuating PA groups. Better outcomes were associated with Emergent and Stable High PA groups. The five BMI trajectories were stable normal/overweight, modest decreasing, fluctuating, steep decreasing, and increasing. No significant interaction existed between PA and BMI trajectories for Mobility Limitations (P= 0.577), Large Muscle Function (P= 0.511), ADLs (P= 0.600), and IADLs (P= 0.152). These findings may empower clinicians to promote messages to midlifers that meaningful changes in PA can improve function in older age.