IMPORTANCE: Because of the negative consequences of concussion, considerable research efforts have been directed toward understanding the risk factors for sport-related concussion (SRC) and its outcomes to better inform strategies for risk reduction. Girls are suggested to have an increased risk of concussion, warranting exploration into sex-dependent variations in concussion presentation and management, with the potential that this information might inform sex-specific rules directed toward risk reduction within sports. OBJECTIVE: To compare sex-associated differences in epidemiology and concussion management in adolescent soccer players within a prospective, longitudinal high school injury surveillance project. DESIGN, SETTING, AND PARTICIPANTS: This prospective, longitudinal cohort study assessed male and female soccer athletes from all high schools in the Michigan High School Athletic Association (MHSAA) during academic years 2016-2017 to 2018-2019. EXPOSURES: Sport-related concussion captured in the MHSAA Head Injury Reporting System. MAIN OUTCOMES AND MEASURES: Outcomes included details regarding each documented SRC event, including injury mechanism, immediate management, and return-to-play time. Multiple comparisons were made between male and female athletes regarding SRC risk, mechanism, short-term management, and outcomes. RESULTS: A total of 43 741 male and 39 637 female soccer athletes participated in MHSAA soccer during the 3 consecutive academic years of study (2016-2017: n = 751 schools; 2017-2018: n = 750 schools; and 2018-2019: n = 747 schools). During the 3 years of surveillance, 1507 of the 83 378 soccer athletes (1.8%) were reported to have SRC during soccer participation, including 557 boys (37.0%) and 950 girls (63.0%). Documented SRC risk in female soccer participants was greater than in male soccer participants (risk ratio, 1.88; 95% CI, 1.69-2.09; P < .001). Male soccer athletes most often sustained SRC from contact with another player (48.4%), whereas SRCs in female soccer players recorded in the Head Injury Reporting System were most often from nonplayer contact events (41.9%; P < .001). Adolescent male soccer players with a documented SRC were more likely to be removed from play on the day of injury (odds ratio, 1.54; 95% CI, 1.15-2.06; P = .004). Although the overall median time to return to play was 11 days (interquartile range [IQR], 7-15 days), male athletes typically returned 2 days earlier than female athletes (median, 10 [IQR, 7-14] days vs 12 [IQR, 7-16] days; Peto test P < .001). CONCLUSIONS AND RELEVANCE: In this cohort study, sex-associated differences were revealed among adolescent soccer athletes in SRC risk, mechanism of injury, immediate management, and outcomes in injuries documented in a statewide injury reporting system. Thus, consideration might be given to sex-specific approaches to participation and concussion management in the sport.