Background: Profiles of substance use among less commonly described subgroups of sexual and gender minority (SGM) people (e.g., queer, genderqueer) remain largely unknown. Objective(s): To identify substance use differences among less commonly described SGM identity-based subgroups. Methods: The PRIDE Study is a national, online, longitudinal cohort study of self-identified SGM adults living in the U.S. Between 2015-2017, an iPhone application was used to administer three cross-sectional health questionnaires to participants, one of which included questions about binge alcohol, marijuana, and other drug use (substance use). This study was a secondary data analysis of participant responses to substance use survey items. Logistic regression and generalized linear modeling assessed relationships between sexual orientation or gender and use of or reported problems with substances within the past year. Results: Among the 1790 participants included in this study, 51.0% reported binge alcohol use, 39.8% reported marijuana use, and 19.7% reported other drug use (65.9% endorsed use of one or more of these) within the past year. Over 30% indicated substance use had been a problem in their life. Asexual individuals had lower odds of reporting past year binge alcohol and marijuana use (aOR: 0.27, 95% CI: 0.12-0.61; aOR: 0.38, 95% CI: 0.15-0.96, respectively), and queer participants had higher odds of reporting past year marijuana use (aOR: 2.52, 95% CI: 1.58-4.03) compared to lesbian participants. Gender nonbinary participants had lower odds of reporting past year binge alcohol use (aOR: 0.48, 95% CI: 0.32-0.71) and transmasculine participants had higher odds of reporting past year marijuana use (aOR: 2.18, 95% CI: 1.10-4.31) compared to cisgender women. Conclusions: Substance use heterogeneity exists between SGM groups. Comprehensive assessment of sexual orientation and gender may improve understanding of substance use and increase equity within support and treatment services for SGM populations. HIGHLIGHTS We examined substance use among less represented sexual and gender minority groups. Alcohol and other drug use were examined by both sexual orientation and gender identity. Analyses included identities such as queer, pansexual, genderqueer and nonbinary. Alcohol use differed across asexual, genderqueer and gender nonbinary groups. Marijuana use differed across queer, asexual and transmasculine groups.