This study builds on existing literature on autism spectrum disorder (autism) and sexual and gender minority (SGM) identities and is the first to examine self-declared frequency rates, associated functional impairments, and treatment engagement levels for sexual minority (SM) and non-SM populations with and without autism cross-sectionally via a large nationwide college-student sample across 3 years. Using data from the American College Health Association-National College Health Assessment (ACHA-NCHA) III, we analyzed data from 81,286 college students (ages 18–25 years old) randomly selected from 75 U.S. colleges and universities. Included ACHA-NCHA-III measures consisted of self-reported demographics, SM and gender minority (GM) identities, autism diagnosis, stress, academic impairment, mental health symptoms, and treatment engagement. We found a 2.8% self-declared frequency of autism in the SM group, compared with 0.9% self-declared frequency among the non-SM sample. Autistic college students with both SM and GM identities had the greatest levels of reported adverse stress and the most negative academic and mental health outcomes (i.e., suicidality), followed by college students with two minority identities (i.e., Autism and SM, SM and GM), across all groups. These findings emphasize the need for mental healthcare providers to consider SM and GM identities in non-autistic and, especially, in autistic college students to assess suicide risk and inform treatment. Lay abstract Autistic individuals and those who identify with a sexual and/or gender minority are both at risk for various mental health concerns and related impairments. However, the connection between autism and sexual and/or gender minorities and mental health and functional outcomes is not clear. Here, we provide evidence of these connections by analyzing data from a large nationally representative dataset from the American College Health Association-National College Health Assessment III. We found that autistic college students who identify with both sexual and gender minorities reported the highest rates of stress, academic, and mental health concerns including suicidality when compared with autistic college students with or without a sexual and/or gender minority. In addition, college students with at least two identities, such as autism and a sexual minority identity or both a sexual and gender minority identity, reported the next highest rates of concern. These findings affirm the need for mental healthcare providers to consider the intersections of a sexual and gender minority identities in non-autistic and, especially, in autistic college students to develop and provide better support and resources.