Objective <p>In the southern United States, adolescents are at elevated risk for HIV acquisition. In Alabama, school-based sexual health and HIV prevention education is strictly regulated and does not address the unique needs of sexual and gender minority (SGM) teenagers. To inform public health efforts, we assessed SGM adolescents’ HIV prevention pre-exposure prophylaxis (PrEP) awareness and modality preferences by gender, race, and ethnicity.</p> Results <p>Survey data were collected in 2023–2024 from SGM adolescents aged 14–17 years, lived in Alabama, with male sex assigned at birth (<i>N</i> = 206). Recruitment occurred online and in-person at a charter school. Data were analyzed using chi-squares and analysis of variance, controlling for age. Over half of respondents were sexually active, but only 26% had ever been tested for HIV. Half knew about PrEP. Of those with PrEP awareness, 41.9% were aware of daily pills; 32.3% of long-acting injectable PrEP. Pill-based PrEP was highly endorsed. Trans- and gender-non-conforming adolescents reported a greater preference for on-demand pill-based PrEP compared to men who have sex with men (<i>p</i> =.01). Non-Hispanics had a greater preference for a 6-month long-acting injectable option compared to Hispanic adolescents (<i>p</i> =.04). Findings suggest the need for HIV prevention interventions tailored to southern contexts and adolescent knowledge.</p> Trial registration <p>Not Applicable.</p>