Lower extremity musculoskeletal injuries are common in sport and exercise, and associated with increased risk of obesity and post-traumatic osteoarthritis (PTOA). Unlike other forms of osteoarthritis, PTOA is common at a younger age and associated with more rapid progression, which may impact career choices, long-term general health and reduce quality of life. Individuals who suffer an activity-related joint injury and present with abnormal joint morphology, elevated adiposity, weak musculature, or become physically inactive are at increased risk of PTOA. Insufficient exercise therapy or incomplete rehabilitation, premature return-to-sport and re-injury, unrealistic expectations, or poor nutrition may further elevate this risk. Delay in surgical interventions in lieu of exercise therapy to optimize muscle strength and neuromuscular control while addressing fear of movement to guarantee resumption of physical activity, completeness of rehabilitation before return-to-sport, education that promotes realistic expectations and self-management, and nutritional counseling are the best approaches for delaying or preventing PTOA.