Black and Latinx transgender youth experience stigma that may increase their susceptibility to mental health symptoms. To compare past-year mental health symptoms and psychosocial factors among Black and Latinx transgender youth, White transgender youth, and Black and Latinx cisgender youth. This survey study used data from the 2015-2017 Biennial California Healthy Kids Survey with a weighted sample (N = 45 269) representative of California's secondary school population. The analytic sample (n = 19 780) included Black and Latinx transgender youth, White transgender youth, and Black and Latinx cisgender youth in the 9th and 11th grades. Data analysis was conducted from July 2020 to February 2021. Outcomes include past-year depressive symptoms and suicidality. Psychosocial risk factors include school-based victimization, gender-based harassment, sexuality-based harassment, and race-based harassment; protective factors include school connectedness and caring adult relationships. The analytic sample of 19 780 participants (in 9th grade: weighted percentage, 51% [95% CI, 50% to 52%]; female participants: weighted percentage, 50% [95% CI, 49% to 51%]) included 252 Black and Latinx transgender youth (weighted percentage, 1.3% [95% CI, 1.1% to 1.5%]), 104 White transgender youth (weighted percentage, 0.7% [95% CI, 0.6% to 0.8%]), and 19 424 Black and Latinx cisgender youth (weighted percentage, 98.0% [95% CI, 97.8% to 98.2%]). For Black and Latinx transgender youth, estimated prevalence of depressive symptoms and suicidality were 50% (95% CI, 44% to 57%) and 46% (95% CI, 39% to 52%), respectively. Logistic regression models adjusted for grade, living arrangement, and reported sex indicated that compared with White transgender youth, Black and Latinx transgender youth had similar odds of depressive symptoms (adjusted odds ratio, 0.6; 95% CI, 0.4 to 1.1) and suicidality (adjusted odds ratio, 1.1; 95% CI, 0.6 to 1.8) and similar odds of all forms of harassment (eg, race-based harassment: adjusted odds ratio, 1.5; 95% CI, 0.8 to 2.6). Regression models indicated that compared with White transgender youth, Black and Latinx transgender youth had similar levels of victimization (adjusted linear regression coefficient, 0.5; 95% CI, -0.3 to 1.3) and caring adult relationships (adjusted linear regression coefficient, -0.6; 95% CI, -1.4 to 0.09) but lower levels of school connectedness (adjusted linear regression coefficient, -1.6; 95% CI, -2.9 to -0.4). With similar analyses, compared with Black and Latinx cisgender youth, Black and Latinx transgender youth had higher odds of depressive symptoms (adjusted odds ratio, 2.7; 95% CI, 2.0 to 3.7) and suicidality (adjusted odds ratio, 5.9; 95% CI, 4.3 to 8.0), higher odds and levels of all forms of harassment and victimization (eg, race-based harassment: adjusted odds ratio, 3.2; 95% CI, 2.4 to 4.5), and lower levels of school connectedness (adjusted linear regression coefficient, -2.6; 95% CI -3.3 to -1.8) and caring adult relationships (adjusted linear regression coefficient, -0.9; 95% CI -1.3 to -0.5). In this study, Black and Latinx transgender youth had high rates of mental health symptoms, with rates comparable with White transgender youth but higher than Black and Latinx cisgender youth. Their unique pattern of psychosocial risk and protective factors for these mental health symptoms should be factored in clinical preventive services and school-based interventions to support them.