Schools play an integral role in creating safe, supportive environments for students, especially for sexual minority youth (SMY). Using 2016 questionnaire data from seven high schools in a Florida school district, we obtained a sample of 1,364 SMY. Logistic regressions controlling for sex (as applicable), age, grade, race/ethnicity, and school explored differences between SMY and nonsexual minority youth (non-SMY). Sex differences related to school environment perceptions and experiences related to safety, bullying, and hearing homophobic remarks were also explored. SMY were more likely than non-SMY to report several negative school environment perceptions and experiences. Where differences existed within SMY, male SMY were more likely than female SMY to have missed school in the past 30 days (odds ratio [OR] = 1.66, p = 0.03), report avoiding spaces at school due to safety concerns (OR = 1.38, p = 0.02), and report hearing homophobic remarks from teachers (OR = 2.00, p = 0.01). Implications for school nursing are discussed.