Considerable evidence suggests that the loss of strength and muscle mass appear to be inevitable consequences of aging. Moreover, aging is associated with an increase in body fat. This study examined whether increased physical activity could prevent or reverse the losses of strength and skeletal muscle mass as well as the gain in fat in older adults. Eleven men and 31 women completed a randomized trial consisting of either a physical activity (PA; n = 22) or successful aging health educational control (SA; n = 20) group. Isokinetic knee extensor strength and computed tomography-derived midthigh skeletal muscle and adipose tissue cross-sectional areas (CSA) were assessed at baseline and at 12 mo following randomization. Total body weight and muscle CSA decreased in both groups, but these losses were not different between groups. Strength adjusted for muscle mass decreased (−20.1 ± 9.3%, P < 0.05) in SA. The loss of strength was completely prevented in PA (+2.5 ± 8.3%). In addition, there was a significant increase (18.4 ± 6.0%) in muscle fat infiltration in SA, but this gain was nearly completely prevented in PA (2.3 ± 5.7%). In conclusion, regular physical activity prevents both the age-associated loss of muscle strength and increase in muscle fat infiltration in older adults with moderate functional limitations.