Stigma and homonegativity contributes to a hostile climate of victimization for LGBTQ individuals inside and outside of school (Katz-Wise & Hyde, 2012; Kosciw, Greytak, Palmer, & Boesen, 2014). Additionally, many LGBTQ youth struggle with increased mental health risk, lower psychological well-being, and poorer school performance (e.g., Haas et al., 2011; Kosciw et al., 2014). Fortunately, researchers have found that feeling supported by school figures can buffer the adverse effects of both LGBTQ-based victimization and prejudice (e.g., Fisher et al., 2008; Kosciw et al., 2014). Using a structural equation model moderation approach with a sample of 235,064 adolescents, this analysis integrates Meyer’s (2003) minority stress model and the buffering hypothesis (Cohen & McKay, 1984) to investigate to what extent self-reported school support may protect against potential effects of marginalized sexual orientation status and/or sexual orientation victimization (SOV; i.e., victimization based on being or being perceived as lesbian or gay). Results indicated that both sexual minority status and SOV significantly predicted negative and psychological outcomes, while school support predicted positive academic and psychological outcomes. Although LGB students reported worse outcomes overall, the negative impact of SOV was significantly greater for heterosexual students’ reports of school safety, School Motivation, Truancy, and Psychological Distress. School Support had a significantly stronger protective effect on heterosexual students’ grades and Psychological Distress, on LGB students’ Truancy, and on non-SOV students’ School Motivation. Lastly, a significant three-way interaction was found between sexual orientation, SOV, and School Support for Psychological Distress, indicating that School Support buffered each group from Psychological Distress, although it appeared to have a greater buffering effect for heterosexual students in comparison to LGB students, particularly comparing LGB students without SOV to heterosexual students with SOV.