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Data are lacking regarding the independent risk of injury related to intense single-sport training or growth rate in young athletes.To determine whether sports specialization, weekly training volumes, and growth rates are associated with increased risk for injury and serious overuse injury in young athletes.Case-control study; Level of evidence, 3.Injured athletes aged 7 to 18 years were recruited from 2 hospital-based sports medicine clinics and compared with healthy controls from affiliated primary care clinics undergoing sports physicals (2010–2013). Participants completed surveys reporting hours per week spent in organized sports, physical education class, and free play, as well as degree of sports specialization and Tanner stage. Heights and weights were measured. Injury details were obtained from athlete surveys and electronic medical records.Of 1214 athletes enrolled, 1190 (50.7% male) had data satisfactory for analysis. There were 822 injured participants (49.5% male; unique injuries, n = 846) and 368 uninjured participants (55% male). Injured athletes were older than uninjured athletes (14.1 ± 2.1 vs 12.9 ± 2.6 years; P < .001) and reported more total hours of physical activity (19.6 ± 9.2 vs 17.6 ± 8.9 h/wk; P < .001) and organized sports activity (11.2 ± 2.6 vs 9.1 ± 6.3 h/wk; P < .01). After accounting for age and hours in sports activity spent per week, sports-specialized training was an independent risk for injury (odds ratio [OR], 1.27; 95% CI, 1.07–1.52; P < .01) and serious overuse injury (OR, 1.36; 95% CI, 1.08–1.72; P < .01). Young athletes participating in more hours of sports per week than number of age in years (OR, 2.07; 95% CI, 1.40–3.05; P < .001) or whose ratio of organized sports to free play time was >2:1 hours/week had increased odds of having a serious overuse injury (OR, 1.87; 95% CI, 1.26–2.76; P < .01). Growth rates were similar between injured and uninjured athletes (4.8 cm/y for both groups; P = .96).Injured young athletes were older and spent more hours per week in organized sports. There is an independent risk of injury and serious overuse injury in young athletes who specialize in a single sport. Growth rate was not related to injury risk. The study data provide guidance for clinicians counseling young athletes and their parents regarding injury risks associated with sports specialization.