Study Design Historical cohort study. Background History of a knee joint injury and increased fat mass are risk factors for joint disease. Objective The objective of this study was to examine differences in adiposity, physical activity, and cardiorespiratory fitness between youths with a 3- to 10-year history of sport-related intra-articular knee injury and uninjured controls. Methods One hundred young adults (aged 15-26 years; 55% female) with a sport-related intra-articular knee injury sustained 3 to 10 years previously and 100 controls matched for age, sex, and sport, who had no history of intra-articular knee injury, were recruited. Fat mass index (FMI) and abdominal fat (fat mass at the L1 to L4 vertebral levels) were derived using dual-energy X-ray absorptiometry. Physical activity and cardiorespiratory fitness were measured using the Godin Leisure-Time Exercise Questionnaire and the multistage 20-meter shuttle run test for aerobic fitness, respectively. Results Previously injured participants demonstrated higher FMI (within-pair difference, 1.05 kg/m; 95% confidence interval [CI]: 0.53, 1.57) and abdominal fat (461 g; 95% CI: 228, 694) than uninjured controls. In multivariable linear regression analysis, previous injury was significantly associated with increased FMI. This increase was attenuated in those who participated in higher levels of physical activity or had higher estimated maximum volume of oxygen. Conclusion As a risk factor for osteoarthritis in an already susceptible group, excess adiposity is an undesirable trait in the potential pathway to joint disease. Increasing physical activity in this population may be a potential intervention to reduce adiposity thus impede disease initiation and/or progression. Level of Evidence Level 2b. J Orthop Sports Phys Ther 2017;47(2):80-87. doi:10.2519/jospt.2017.7101.