Objective: To compare short-term changes in knee-related quality of life (QOL) and associated clinical outcomes between youth with and without a sport-related knee injury. Design: Prospective cohort study. Setting: Sport medicine and physiotherapy clinics. Participants: Youth (11-19 years old) who sustained an intra-articular, sport-related knee injury in the past 4 months and uninjured youth of similar age, sex, and sport. Independent Variable: Injury history. Main Outcome Measures: Knee-related QOL (Knee injury and Osteoarthritis Outcome Score, KOOS), knee extensor and flexor strength (dynamometry), physical activity (accelerometer), fat mass index (FMI; bioelectrical impedance), and kinesiophobia (Tampa Scale for Kinesiophobia, TSK) were measured at baseline (within 4 months of injury) and at 6-month follow-up. Wilcoxon rank sum tests assessed between-group differences for all outcomes. Regression models assessed the association between injury history and outcome change (baseline to 6-month follow-up), considering sex. The influence of injury type, baseline values, and physiotherapy attendance was explored. Results: Participants' (93 injured youth, 73 uninjured control subjects) median age was 16 (range 11-20) years and 66% were female. Despite greater improvements in KOOS QOL scores (20; 95% confidence interval, 15-25), injured participants demonstrated deficits at 6-month follow-up (z = 9.3, P < 0.01) compared with control subjects, regardless of sex. Similar findings were observed for knee extensor and flexor strength and TSK scores but not for physical activity or FMI. Lower baseline values were associated with greater outcome changes in injured youth. Conclusions: Youth have worse knee-related QOL, muscle strength, and kinesiophobia early after a sport-related knee injury than control subjects. Despite improvements, deficits persist 6 months later.