At-risk adolescents may experience Social Determinants of Health (SDoH) that lead to higher rates of risky sexual behavior, including increased risk of pregnancy and sexually transmitted infections. These SDoH may include components such as unstable family structures, incomplete education, and poverty. Targeting at-risk youth for sexuality education is one way to work toward decreasing sexual health disparities. However, preferences for sexuality education approaches may differ among at-risk youth by additional factors including sex and sexual orientation. The purpose of this study was to describe sexuality education preferences among at-risk youth and how sexuality education preferences differ based on sex and sexual orientation in an at-risk sample of high school-aged youth in Texas. Results indicate sexuality education preferences differ based on sex and sexual orientation when examined by sexual health topics and methods of delivery. Implications of this study indicate including at-risk youth in sexual health programs may be a way to target those at-risk of adverse SDoH, but these groups also have specific preferences for sexuality education.