Objectives: Lesbian, gay, and bisexual (LGB) populations exhibit elevated rates of psychiatric disorders compared to heterosexuals, and these disparities emerge early in the life course. We examined the role of exposure to early-life victimization and adversity--including physical and sexual abuse, homelessness, and intimate partner violence--in explaining sexual orientation disparities in mental health among adolescents and young adults. Methods: Data were drawn from the National Longitudinal Study of Adolescent Health, Wave 3 (2001-2002), a nationally representative survey of adolescents. Participants included gay/lesbian (n=227), bisexual (n=245), and heterosexual (n=13,490) youths, ages 18-27. We examined differences in the prevalence of exposure to child physical or sexual abuse, homelessness or expulsion from one's home by caregivers, and physical and sexual intimate partner violence according to sexual orientation. Next we examined the associations of these exposures with symptoms of psychopathology including suicidal ideation and attempts, depression, binge drinking, illicit drug use, tobacco use, alcohol abuse, and drug abuse. Finally, we determined whether exposure to victimization and adversity explained the association between sexual orientation and psychopathology. Results: Gay/lesbian and bisexual respondents had higher levels of psychopathology than heterosexuals across all outcomes. Gay/lesbian respondents had higher odds of exposure to child abuse and housing adversity, and bisexual respondents had higher odds of exposure to child abuse, housing adversity, and intimate partner violence, than heterosexuals. Greater exposure to these adversities explained between 10 and 20% of the relative excess of suicidality, depression, tobacco use, and symptoms of alcohol and drug abuse among LGB youths compared to heterosexuals. Exposure to victimization and adversity experiences in childhood and adolescence significantly mediated the association of both gay/lesbian and bisexual orientation with suicidality, depressive symptoms, tobacco use, and alcohol abuse. Conclusions: Exposure to victimization in early-life family and romantic relationships explains, in part, sexual orientation disparities in a wide range of mental health and substance use outcomes, highlighting novel targets for preventive interventions aimed at reducing these disparities. (Contains 4 tables.)