Despite efforts to recruit and retain Black physicians, Black individuals continue to be underrepresented in medicine in the USA. Although numerous studies have investigated the experiences of academic physicians from racial/ethnic backgrounds underrepresented in medicine, the experience of Black academic physicians, who may face additional unique challenges, remains underinvestigated. Using a qualitative research design, we investigate barriers to and facilitators of success and well-being of Black faculty at one academic medical center through interviews of 30 Black faculty members. Overall, ten themes emerged as barriers or facilitators to faculty success and well-being. Significant barriers include continued lack of representation; devaluing of research in community health and health disparities, as well as other diversity-related activities; and both overt and implicit discrimination, which contribute to feelings of isolation and disrespect. Facilitators include having a community to maintain sense of belonging, financial support for health disparities and diversity-related contributions, and collaboration with peers. Good mentorship and sponsorship as well as an institutional culture that supports inclusion can play significant roles as facilitators, whereas the lack of these factors can present substantial barriers. Institutional policies and external socio-political factors have a major influence on both the barriers and facilitators to the success and well-being of Black faculty. Our study has put a clearer focus on barriers that are unique to or more pronounced among Black faculty and the facilitators that may serve to mitigate these barriers. These findings can inform the design of interventions to recruit and retain Black faculty in medicine.