Free-living wildlife across Africa is found across expansive rangelands, frequently interacting with pastoral communities, their livestock, and domestic dogs (Canis familiaris). African wildlife populations are threatened by development, poaching and disease. Infectious diseases have caused significant declines, sabotaging conservation efforts. Canine distemper virus (CDV) infections have increased in incidence in wildlife over the past four decades. Sympatric domestic dogs have been presumed to be the reservoirs of the virus for wildlife. A systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines was carried out to investigate CDV infections in wildlife in Africa, to 1) analyze the conservation concerns associated with the disease, 2) identify the dynamics of the virus across different ecoregions, and 3) ascertain the source of the virus for free-living wildlife. The database searches identified 65 articles relevant to the study questions and an additional 43 valuable for wider discussion of the topic area. Canine distemper outbreaks were reported to occur in wildlife in six African countries, with mortality rates between 30% and 94% across all species affected. Eleven wildlife species were identified as susceptible, 64% of which (7/11) are classified as threatened by the International Union for Conservation of Nature. Disease dynamics varied between ecoregions because of differences in land use; virus strains; climate change and concurrent infections; ecotones; domestic and wildlife population densities; wildlife monitoring capacity; and wildlife movement. Nine countries reported outbreaks in domestic dog populations in or near wildlife habitats, but none reported confirmed transmission to wildlife. Of 23 reports investigating the role of domestic dogs as CDV reservoirs, 14 (61%) concluded that domestic dogs acted as either reservoirs or sources of CDV for wildlife, four (17%) did not identify dogs as reservoirs, and five (22%) were not sure of the role played by domestic dogs. This review highlights the importance of integrating active CDV surveillance in wildlife conservation programs.