This study tested the mechanisms by which social stigma contributes to psychological distress in lesbian, gay, and bisexual individuals. A large community sample (N = 4248, M age = 29.9 years, 42.9% female, 57.1% male, 35.7% bisexual, 64.3% lesbian/gay, 9.9% non-white) was recruited using targeted and general advertisements for an online cross-sectional survey. Participants completed measures of childhood gender nonconformity, prejudice events, victimization, microaggressions, sexual orientation concealment, sexual orientation disclosure, expectations of rejection, self-stigma, rumination, and distress. Structural equation modeling was used to test the relationships between these variables in a model based upon minority stress theory and the integrative mediation framework with childhood gender nonconformity as the initial independent variable and distress (depression, anxiety, and well-being) as the final dependent variable. The results broadly support the hypothesized model. The final model had good fit χ 2 (37) = 440.99, p < .001, TLI = .96, CFI = .98, RMSEA = .05 [.05, .06] and explained 50.2% of the variance in psychological distress and 24.8% in rumination. Sexual orientation and gender had moderating effects on some individual paths. Results should be considered in the context of the cross-sectional nature of the data, which prevented tests of causality, and self-report measures used, which are vulnerable to bias. Findings indicate strong relationships between minority stressors and psychological distress in lesbian, gay, and bisexual individuals, which are partially accounted for by rumination. These results may inform the development of interventions that address the added burden of minority stress among lesbian, gay, and bisexual individuals.