Objectives. We examined the associations between 3 types of discrimination (sexual orientation, race, and gender) and substance use disorders in a large national sample in the United States that included 577 lesbian, gay, and bisexual (LGB) adults. Methods. Data were collected from wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, which used structured diagnostic face-to-face interviews. Results. More than two thirds of LGB adults reported at least 1 type of discrimination in their lifetimes. Multivariate analyses indicated that the odds of past-year substance use disorders were nearly 4 times greater among LGB adults who reported all 3 types of discrimination prior to the past year than for LGB adults who did not report discrimination (adjusted odds ratio = 3.85; 95% confidence interval = 1.71, 8.66). Conclusions. Health professionals should consider the role multiple types of discrimination plays in the development and treatment of substance use disorders among LGB adults.