Transgender and gender diverse youth (TGD) report high rates of mental health concerns. However, there is reason to expect that among TGD youth there is variation in mental health experiences related to specific aspects of gender identity. Furthermore, although certain school characteristics are related to improved mental health for sexual minority youth, it is unclear whether the same school characteristics are associated with improved mental health for TGD youth and whether gender identity moderates the associations between school characteristics and mental health. Using baseline data from Project AVANT, a longitudinal study of TGD youth ages 14–18 years in the United States (N = 252), we report on several mental health outcomes (i.e., depression, anxiety, nonsuicidal self-injury, and PTSD), with attention to differences by gender identity. Secondly, we examined associations of three protective school-related factors (i.e., school-connectedness, presence of a Gay-Straight or Gender-Sexuality Alliance [GSA], and state mandated protections for sexual and gender minority students) with TGD youth mental health. TGD youth reported elevated levels of anxious and depressive symptoms, with nonbinary youth assigned female at birth reporting higher mean depressive symptoms relative to transgender females. Among the aggregate sample of TGD youth, 69.9% reported clinically significant anxiety, 57.9% reported clinically significant depression, 56.7% reported nonsuicidal self-injury, and 46.4% met screening criteria for posttraumatic stress disorder. Despite a small effect size, greater school-connectedness was significantly associated with fewer mental health concerns and gender identity moderated the association between school-connectedness and number of anxiety symptoms. Gender identity also moderated the association between presence of a GSA and number of anxious symptoms, depressive symptoms, and clinically significant depression, respectively. No significant associations of state-level protections and mental health outcomes were detected. Findings highlight the importance of improving mental health and fostering GSA-engagement and school-connectedness among TGD youth. Implications for school psychologists are discussed.