Background Lesbian, gay, bisexual and transgender (LGBT) youth have a higher risk of suicidality and self-harm than heterosexual youth populations but little is known about the underlying mechanisms. We aimed to investigate the social determinants of this mental health inequality. Methods A two-stage sequential mixed method study was conducted. Firstly, 29 semi-structured interviews with LGBT youth (aged 13–25 years old) were completed. Data was analysed thematically. Stage 2 involved a self-completed questionnaire employing an online community-based sampling strategy (n = 789). Logistic regression analysis was performed to predict suicidality. Results Five social determinants explained suicidal risk: (i) homophobia, biphobia or transphobia; (ii) sexual and gender norms; (iii) managing sexual and gender identities across multiple life domains; (iv) being unable to talk; (v) other life crises. Youth who were transgender (OR = 1.50, P < 0.022), disabled (OR = 2.23, P < 0.000), had self-harmed (OR = 7.45, P < 0.000), were affected by abuse (OR = 2.14, P < 0.000), and affected by not talking about their emotions (OR = 2.43, P < 0.044) were most likely to have planned or attempted suicide. Conclusions Public health universal interventions that tackle bullying and discrimination in schools, and selected interventions that provide specific LGBT youth mental health support could reduce LGBT mental health inequalities in youth suicidality.