Homophobic name-calling and sexual violence are prevalent among US high school students and have been associated with a host of negative consequences including anxiety, depression, and substance use disorders, especially among sexual and gender minority youth. Although homophobic name-calling and sexual violence are linked to common risk and protective factors, most prior studies have failed to include gender and sexual minority groups. The present study used path analyses to explore the associations between eight protective factors and the outcomes of homophobic name-calling perpetration, homophobic name-calling victimization, sexual violence perpetration, and sexual violence victimization. The sample included LGB (n = 938), transgender (n = 140), and heterosexual (n = 3,744) high school students in Colorado, USA (N = 4,822). Protective factors included: (1) family support; (2) peer support; (3) friendships with trusted adults; (4) participating in healthy activities; (5) helping others; (6) spirituality; (7) access to counseling; and (8) access to medical services. For homophobic name-calling perpetration and victimization, significant negative associations emerged across different groups for the protective factors of family support, peer support, helping others, spirituality, counseling, and medical access. For sexual violence perpetration and victimization, significant negative associations emerged across different groups for the protective factors family support, peer support, and counseling access. Findings suggest that prevention and intervention efforts to address gender-based harassment should focus on building protective, supportive environments across the schools, families, and communities.