Early degenerative changes in the knee cartilage of people aged 45–60 years without symptoms of osteoarthritis are greatest in those who exercise more or less than average. 205 participants in the normal and incidence cohorts of the Osteoarthritis Initiative, who had Kellgren–Lawrence scores <2 at baseline, had their cartilage T2 relaxation times assessed by MRI after 2 and 4 years. Greater T2 progression—denoting increased damage—occurred in various knee compartments in those who scored in the highest tertile or lowest 15% of results from the Physical Activity Scale for the Elderly questionnaire, compared with the middle tertile (and adjusted for age, sex and BMI). Activity scores were obtained annually for 4 years. All tertiles showed T2 progression during the study, suggesting that biochemical degeneration of the cartilage matrix accelerates over time.