Background: Sports-related concussions may have a neurobiological recovery period that exceeds the period of clinical recovery, and one consequence of an extended neurobiological recovery may be the risk of subsequent musculoskeletal injuries. Most literature citing an increased risk of musculoskeletal injury after a sports-related concussion has been reported in populations other than adolescent athletes. Purpose/Hypothesis: The purpose was to prospectively determine if incidence rates of musculoskeletal injury differ between adolescent athletes with and without a previous sports-related concussion, while controlling for sex, sport, and age. A secondary aim was to determine if this relationship differs between male and female athletes of the same sport. Our hypotheses were that acute-noncontact injury rates would be higher in athletes with a previous sports-related concussion when compared with athletes without a previous sports-related concussion, and that this relationship would exist only in female athletes and not male athletes. Study Design: Cohort study; Level of evidence, 2. Methods: High school soccer and volleyball players were recruited in 2 prospective cohort studies that observed 4837 athletes during their sporting season (females, 80%; soccer, 57%; mean [SD] age, 15.6 [1.1] years). At preseason, all participants self-reported demographics and previous sports-related concussion within the past 12 months. During the sport season, team athletic trainers electronically recorded athlete exposures and injury data, including injury characteristics. Injury rates per 1000 athlete exposures and injury rate ratios (IRRs) with 95% confidence intervals were calculated. All injury rates and IRRs were adjusted for sex, age, and sport. Results: The rate of acute-noncontact lower extremity injury was 87% greater (IRR, 1.87; 95% CI, 1.29-2.74) in participants with a previous sports-related concussion versus those without one. The acute-noncontact lower extremity injury rates (IRRs) for females and males with a previous sports-related concussion were 1.76 (95% CI, 1.19-2.59) and 2.83 (95% CI, 0.85-9.50), respectively. No difference was detected in acute-contact (IRR, 0.98; 95% CI, 0.56-1.73) or overuse (IRR, 1.09; 95% CI, 0.51-2.37) lower extremity injury rates by previous sports-related concussion. Conclusion: Female adolescent athletes who reported a sports-related concussion within the past 12 months were more likely to sustain an acute-noncontact lower extremity injury during their high school sports season when compared with female athletes without a previous sport-related concussion.