HIV remains a public health concern in the United States. Although pre-exposure prophylaxis (PrEP) can be expected to reduce HIV incidence, its uptake, adherence, and persistence remain limited, particularly among highest priority groups such as men who have sex with men and transwomen (MSMTW). Using a socioecological framework, we conducted a scoping review to examine PrEP-related stigma to inform future research, policy, and programmatic planning. Using the PRISMA extension for scoping reviews, we conducted database searches from August 2018 to April 2020 for articles addressing PrEP stigma. Studies were independently screened and coded by three authors, resulting in thematic categorization of several types of PrEP stigma on four socioecological levels. Of 557 references, a final sample of 23 studies was coded, 61% qualitative, and 87% focusing exclusively on MSMTW. Most instances of PrEP-related stigma occurred on the interpersonal level and included associations of PrEP with risk promotion, HIV-related stigma, and promiscuity. Other frequent themes across socioecological levels included provider distrust and discrimination, government and pharmaceutical industry distrust, internalized homonegativity, PrEP efficacy distrust, and anticipated homonegativity. Notably, PrEP was also framed positively as having physical and psychological benefits, and assuming responsibility for protecting one's community via PrEP awareness-raising. PrEP-related stigma persists, demanding interventions to modify its impact. Leveraging PrEP-positive discourses to challenge PrEP stigma is an emerging avenue, alongside efforts to increase provider willingness to promote PrEP routinely by reducing provider bias, aligning with the national strategy to End the HIV Epidemic.