Background: In the face of health-system constraints, local policymakers and decision-makers face difficult choices about how to implement, expand and institutionalize antiretroviral therapy (ART) services. This scoping review aimed to describe the barriers and facilitators to the implementation and scale up of differentiated service delivery (DSD) models for HIV treatment in Africa. Methods: PubMed, Web of Science, Embase, Scopus, CINAHL, Global Health, Google, and Google Scholar databases were searched. There was no start date thereby all references up until May 12, 2021, were included in this review. We included studies reported in the English language focusing on stable adult people living with human immune deficiency virus (HIV) on ART and the healthcare providers in Africa. Studies related to children, adolescents, pregnant and lactating women, and key populations (people who inject drugs, men having sex with men, transgender persons, sex workers, and prisoners), and studies about effectiveness, cost, cost-effectiveness, and pre or post-exposure prophylaxis were excluded. A descriptive analysis was done. Results: Fifty-seven articles fulfilled our eligibility criteria. Several factors influencing DSD implementation and scale-up emerged. There is variability in the reported factors across DSD models and studies, with the same element serving as a facilitator in one context but a barrier in another. Perceived reduction in costs of visit for patients, reduction in staff workload and overburdening of health facilities, and improved or maintained patients’ adherence and retention were reported facilitators for implementing DSD models. Patients’ fear of stigma and discrimination, patients’ and providers’ low literacy levels on the DSD model, ARV drug stock-outs, and supply chain inconsistencies were major barriers affecting DSD model implementation. Stigma, lack of model adoption from providers, and a lack of resources were reported as a bottleneck for the DSD model scale up. Leadership and governance were reported as both a facilitator and a barrier to scaling up the DSD model. Conclusions: This review has important implications for policy, practice, and research as it increases understanding of the factors that influence DSD model implementation and scale up. Large-scale studies based on implementation and scale up theories, models, and frameworks focusing on each DSD model in each healthcare setting are needed.