Transgender (trans) and non-binary people may be at increased risk of alcohol harms, but little is known about motives for drinking in this community. This study explored the relationship between risk of alcohol dependence, experience of alcohol harms, drinking motives, dysphoria, and discrimination within a United Kingdom sample of trans and non-binary people with a lifetime history of alcohol use. A cross-sectional survey was co-produced with community stakeholders and administered to a purposive sample of trans and non-binary people from 1 February until 31 March 2022. A total of 462 respondents were included-159 identified as non-binary and/or genderqueer (identities outside the man/woman binary), 135 solely as women, 63 solely as men, 15 as another gender identity, 90 selected multiple identities. Higher levels of reported discrimination were associated with higher risk of dependence and more reported harms from drinking. Coping motives, enhancement motives, and drinking to manage dysphoria were associated with higher Alcohol Use Disorders Identification Test scores. Social, coping, and enhancement motives alongside discrimination and drinking to have sex were associated with harms. The relationship between discrimination and risk of dependence was mediated by coping motives and drinking to manage dysphoria. Further to these associations, we suggest that reducing discrimination against trans and non-binary communities might reduce alcohol harms in this population. Interventions should target enhancement motives, coping motives and gender dysphoria. Social and enhancement functions of alcohol could be replaced by alcohol free supportive social spaces.