Introduction Discrimination related to gender identity may directly influence vulnerability to HIV through increased exposure to unprotected receptive anal intercourse (URAI). Little is known about the relationship between gender-based discrimination (GBD) and URAI with stable partners among transgender women. Methods This mixed-methods research began with a cross-sectional survey conducted between 2014 and 2016 with transgender women in Salvador, the capital city in one of the poorest regions in Brazil. Respondent-driven sampling was used to recruit the study population. GBD was defined through Latent Class Analysis. Additionally, 19 semi-structured interviews with participants were transcribed and analyzed through thematic content analysis. Results URAI with stable partners was commonly reported (37.3%). GDB was positively associated with URAI among stable partners (OR = 6.47; IC 95%: 1.67–25.02). The analysis of the interviews illustrated how GBD impacted transgender women in diverse ways. Experiences with GBD perpetrated by the family often initiated a trajectory of economic vulnerability that led many to engage in survival sex work. The constant experience with GBD contributed to participants feeling an immense sense of trust with their stable partners, ultimately diminished their desire to use condoms. Further, the high frequency of GBD contributed to poor mental health overall, though some participants said engagement in transgender advocacy efforts provided a vital source of resilience and support.