HIV remains a threat to global public health, disproportionately affecting countries across Sub-Saharan Africa. Although treatment and access to care have improved, prevention remains critical to ending new HIV infections by 2030. A variety of prevention strategies exist, yet their effectiveness is difficult to measure and variable due to the nature of the interventions and vulnerability of the intervention during implementation. This systematic review of 51 studies synthesizes data on the implementation and evaluation of evidence-based HIV prevention interventions across Sub-Saharan Africa. Studies were included if they occurred between January 1, 2008, and December 31, 2019, inclusive in Sub-Saharan Africa, were written in English, implemented an HIV prevention intervention in the field, and had reportable results. Using a modified social-ecological model for HIV prevention, we divided studies into three categories: interventions targeting health systems (n = 16), communities (n = 8), and individuals (n = 27). Across all categories, the data emphasized preventing mother-to-child transmission (PMTCT), medical interventions, and psychosocial interventions. The most successful programs bundled several interventions that were integrated into the health system. There is a notable lack of interventions targeting key populations and there are significant rates of loss to follow up (LTFU) across many studies. This review provides insight into the prioritization of evidence-based HIV prevention interventions across Sub-Saharan Africa.