Purpose The objective of this study is to determine incidence (injuries/1000 playing hours (ph)), severity (days of absence), and cause of match injuries in US women's Rugby-7s. Methods We performed a prospective epidemiological study (2010-2013) of injury of 3876 under-19 to elite/national female Rugby-7s players (nonelite = 3324, elite = 552) on 323 teams (nonelite = 277, elite = 46), applying methodology and injury definitions compliant with the international consensus statement on rugby research. Injuries occurred in USA Rugby-sanctioned tournament series: USA Rugby Local Area (2010), Territorial Union (2011-2013), National and All-Star Sevens Series, and USA Sevens Invitational (2011-2012) and Collegiate Rugby Championships (2012). Results One hundred and twenty time-loss injuries were encountered (elite, n = 15; 13%) with an injury rate of 46.3 injuries/1000 ph. Injury rates in nonelite were 49.3/1000 ph, and in national level (elite) candidates, 32.6/1000 ph (RR = 1.5, P = 0.130). Mean days missed found elite level players at 74.9 d per injury, whereas nonelite at 41.8 d (P = 0.090). Acute injuries were significant (95%, RR = 1.9, P < 0.001), resulting in immediate removal from the pitch (56%, P < 0.001). The main mechanism of injury occurred when tackling players (73%, P < 0.001). The most common type of injury seen were ligament sprains (37%, 13.9/1000 ph), involving the lower extremity (45%, 20.5/1000 ph). The most common body parts injured were the knee and head/face (16%, 7.3/1000 ph). Conclusions Time-loss injuries occurred with frequency in the US women's Rugby-7s tournaments. Overall injury rates in US women are lower than those in international elite men and women's Rugby-7s. The head and neck area in our female players was injured at greater rates (16%) than in international male Rugby-7s (5%). Injury prevention in US women's Rugby-7s must focus on injuries of the knee, head, and neck. Understanding risk factors will allow safe return-to-play decisions and formulate injury prevention protocols.