Abstract Introduction The multidimensionality of stigma that LGBT people experience globally necessitates research to explore the processes at work. The study aimed to quantify the level of othering and explore the process of LGBT othering in Rwanda. Methods We conducted a sequential cross-sectional mixed-methods study of LGBT lived experiences in Rwanda. We recruited 499 participants to complete the LGBT-specific survey and 1254 for the non-LGBT survey. We conducted 16 in-depth interviews (IDIs) with non-LGBT participants. For LGBT participants, we completed six focus groups with 59 participants, six in-depth interviews, and three digital storytelling interviews. For the quantitative surveys, we conducted multivariable linear regressions and reported beta coefficients and 95% confidence interval estimates examining LGBT discrimination (LGBT survey) and attitudes toward LGBT (non-LGBT survey). We used deductive and inductive thematic and narrative analysis to analyze the qualitative data. Results In adjusted analyses of the non-LGBT survey, as compared to those who knew zero LGBT persons, persons who knew more than five had lower negative attitude scores (β = − 1.3, 95% CI − 2.2, − 0.5), while the score was lower for those that knew one to five (− 0.2), it was not significant (95% CI − 0.8, 0.5). In the LGBT survey, adjusted analyses indicated that there was no significant difference found in discrimination between bisexual, gay, or lesbian participants. However, as compared to cisgender participants, transgender participants had discrimination scores that were 2.1 points higher (95% CI 1.1, 3.0), and gender non-confirming individuals had scores that were one point higher (95% CI 0.2, 1.9). The qualitative findings showcased how societal “othering” occurs in the everyday life of LGBT Rwandans, with large ramifications in creating feelings of isolation and hampering one’s capacity to live authentically and with dignity. Conclusion The findings from our study indicate a high level of othering of the LGBT community across multiple domains, including housing, employment, healthcare, education, religion, and family within Rwanda. Policy Implications The findings highlight the importance of social education campaigns about LGBT people, particularly among vital societal role-holders, including healthcare providers and educators. Integrating the rich historical and indigenous culture related to LGBT could be successful in combating anti-West rhetoric.