Cisgender Black women (CBW) experience 67% of new HIV diagnoses among women in the South. Progress toward ending the HIV epidemic requires researchers to explore perceptions of factors related to the decision to initiate pre-exposure prophylaxis (PrEP) among CBW. Qualitative methods were used to explore how social and structural constructs influence individual decisions to use PrEP among 20 CBW through focus groups. The thematic data analysis identified how facilitators and barriers to PrEP uptake aligned with an external locus of control (LOC) [e.g., media influences on understanding of PrEP] or an internal LOC (e.g., awareness of personal vulnerability to HIV). Several participants highlighted that their PrEP knowledge was rooted in an external LOC, such as media campaigns. A participant stated, ‘But even with the commercial, it wasn’t representation for me.’ Another participant described her personal HIV vulnerability in her sexual relationship as an internal LOC, stating, ‘Not ignorance, it’s maybe just not accepting the true reality of this can be contracted even from someone that you believe that you trust.’ Due to gaps in media marketing, healthcare providers should be aware that some female patients may perceive that PrEP is not for them. Provider-led sexual health discussions are urgently needed to bridge the gap between PrEP eligibility and initiation.