Men who have sex with men (MSM) and female sex workers (FSW) are increasingly and disproportionately impacted by HIV in sub-Saharan Africa, yet current PrEP care models in this region are not optimized for these communities. Limited data exist describing experiences and preferences of MSM and FSW with respect to accessing and using PrEP. We conducted qualitative, semi-structured interviews with MSM and FSW recruited from three health centers and seven community organizations in Kigali, Rwanda. Data were analyzed using a mixed deductive and inductive approach to describe key themes related to initiating and adhering to PrEP. Participants included 18 MSM and 14 FSW; 12 were using PrEP at the time of interview, 9 had previously used PrEP, and 11 had never used it. Participants highlighted the central role of their social networks as key sources of information about and support for PrEP use, and described a strong motivation to use PrEP as a way to protect both themselves and their communities from HIV. While stigma and discrimination were pervasive, these were experienced differently by MSM and FSW. Participants suggested community access points that allowed more discreet and less frequent contact with health care workers as important and desired strategies to improve engagement. These findings suggest that leveraging community resources for disseminating information about HIV prevention and delivering PrEP could contribute to successful implementation of PrEP for MSM and FSW in Rwanda and other settings in SSA.