There is a paucity of population health data on the experiences of transgender, non-binary, and other gender minority gay, bisexual, and queer men, and Two-Spirit people in Canada. To address this gap, this article presents a socio-demographic and health profile of trans and non-binary participants from the community-based bilingual 2018 Sex Now Survey. Participants were recruited in-person from Pride festivals in 15 communities to self-complete an anonymous paper-and-pen questionnaire. To be eligible, participants needed to be at least 15 years old, live in Canada, either report a non-heterosexual sexual identity or report sex with a man in the past 5 years, and not report gender identity as a woman. Through community consultations the survey was inclusive of trans men, non-binary people, and Two-Spirit people. Three gender groups (cisgender, transgender, and non-binary) were created, and trans and non-binary participants were compared with their cisgender peers across a variety of demographic, mental health, sexual health, and general health indicators. Odds ratios were calculated to determine initial significance for categorical variables, and adjusted odds ratios were calculated to control for five possible confounders (age, ethnoracial identity, country of birth, sexual identity, and financial strain). Significant differences emerged across all sets of indicators, with many of these findings remaining significant after adjusting for confounding variables, including significantly higher reported rates of mental health challenges and sexual health service barriers for trans and non-binary participants compared to the cisgender group. Trans and non-binary participants were also more likely to be in polyamorous relationships. Collectively, our findings demonstrate that trans and non-binary people experience significant disadvantages compared with cisgender sexual minority men. Improved educational supports and employment protections, access to queer and gender affirming healthcare, and trauma-informed mental health services are needed to improve the health wellbeing of trans and non-binary people in Canada.