Globally, research indicates that LGBTQ+ young people have elevated rates of poor mental health in comparison with their cisgender heterosexual peers. The school environment is a major risk factor and is consistently associated with negative mental health outcomes for LGBTQ+ young people. The aim of this UK study was to develop a programme theory that explained how, why, for whom, and in what context school-based interventions prevent or reduce mental health problems in LGBTQ+ young people, through participation with key stakeholders. Online realist interviews were conducted in the UK with (1) LGBTQ+ young people aged between 13–18 years attending secondary schools (N = 10); (2) intervention practitioners (N = 9); and (3) school staff (N = 3). A realist retroductive data analysis strategy was employed to identify causal pathways across different interventions that improved mental health outcomes. The programme theory we produced explains how school-based interventions that directly tackle dominant cisgender and heterosexual norms can improve LGBTQ+ pupils’ mental health. We found that context factors such as a ‘whole-school approach’ and ‘collaborative leadership’ were crucial to the delivery of successful interventions. Our theory posits three causal pathways that might improve mental health: (1) interventions that promote LGBTQ+ visibility and facilitate usualising, school belonging, and recognition; (2) interventions for talking and support that develop safety and coping; and (3) interventions that address institutional school culture (staff training and inclusion polices) that foster school belonging, empowerment, recognition, and safety. Our theoretical model suggests that providing a school environment that affirms and usualises LGBTQ+ identities and promotes school safety and belonging can improve mental health outcomes for LGBTQ+ pupils.