BACKGROUND: Intersectionality theory focuses on how one's human experiences are constituted by mutually reinforcing interactions between different aspects of one's identities, such as race, class, gender, and sexual orientation. In this study, we asked: 1) Do associations between intersecting identities (race and sexual orientation) and mental health (depressive symptoms) and substance use (alcohol, tobacco, and marijuana) differ between men and women? and 2) How do single or intersecting self-reports of perceived racial and/or sexual orientation discrimination influence mental health and substance use outcomes for men and women? We compared results of assessing identities versus experiences of discrimination. METHODS: Multivariable regressions were conducted on cross-sectional data from 2315 Black and White college students. Predictors included measures of sociodemographic characteristics and experiences of discrimination. Outcomes included past 2-week depressive symptoms (PHQ-9), past 30-day alcohol use, past 30-day tobacco use, and past 30-day marijuana use. RESULTS: Intersecting identities and experience of discrimination had different associations with outcomes. Among women, self-reporting both forms of discrimination was associated with higher depressive symptoms and substance use. For example, compared to women experiencing no discrimination, women experiencing both forms of discrimination had higher depressive symptoms (B = 3.63, CI = [2.22-5.03]), alcohol use (B = 1.65, CI = [0.56-2.73]), tobacco use (OR = 3.45, CI = [1.97-6.05]), and marijuana use (OR = 3.38, CI = [1.80-6.31]). However, compared to White heterosexual women, White sexual minority women had higher risks for all outcomes (B = 3.16 and CI = [2.03-4.29] for depressive symptoms, B = 1.45 and CI = [0.58-2.32] for alcohol use, OR = 2.21 and CI = [1.32-3.70] for tobacco use, and OR = 3.01 and CI = [1.77-5.12] for marijuana use); while Black sexual minority women had higher tobacco (OR = 2.64, CI = [1.39-5.02]) and marijuana use (OR = 2.81, CI = [1.33-5.92]) only. Compared to White heterosexual men, White sexual minority men had higher depressive symptoms (B = 1.90, CI = [0.52-3.28]) and marijuana use (OR = 2.37, CI = [1.24-4.49]). CONCLUSIONS: Our results highlight the deleterious impacts of racial discrimination and sexual orientation discrimination on health, in particular for women. Future studies should distinguish between and jointly assess intersecting social positions (e.g., identities) and processes (e.g., interpersonal experience of discrimination or forms of structural oppression).