Epstein–Barr Virus (EBV) is a widespread human herpesvirus known for causing infectious mononucleosis and being linked to several cancers, including Burkitt lymphoma and nasopharyngeal carcinoma—both of which are prevalent in parts of Sub-Saharan Africa. The virus is transmitted primarily through saliva and remains dormant in the body after infection, with reactivation risks increasing in immunocompromised individuals. In Sub-Saharan Africa, EBV’s interaction with malaria and HIV infections amplifies its clinical impact, making awareness and early diagnosis essential. Strengthening laboratory capacity and public health education can help reduce EBV-related complications across the region.