Vaccine-preventable diseases (VPDs) pose a significant threat to public health, particularly in poor, marginalised areas of Africa. The prevalence of VPDs varies across countries due to factors like climate and host adaptations. The Vaccine Alliance (GAVI) has contributed to increased vaccination rates in low- and middle-income countries (LMICs) in Asia and Africa. The Expanded Program on Immunization (EPI) has significantly improved Africa’s vaccination rate, with countries like Nigeria, Ethiopia, Uganda, and Ghana seeing increased vaccine coverage. VPDs include rotavirus-linked diarrhoea, Japanese encephalitis, dengue fever, rabies, polio, hepatitis (A, B, and E), and yellow fever. The high prevalence of VPDs in sub-Saharan Africa is attributed to factors such as low vaccination rates, limited healthcare access, slow vaccine adoption, and underlying socioeconomic and environmental conditions. The 2020 SARS-CoV-2 outbreak disrupted routine medical care facilities and immunisation programs, potentially contributing to a drop in vaccine coverage. Strategic investments in strengthening health systems are essential for effective immunisation against VPDs. This chapter critically discusses critical viral-originating VPDs, their epidemiology, public health impact, and ongoing vaccination programs. It also discusses losses averted by vaccination programmes, surveillance systems, machine learning, and global collaborative efforts.