The Eocene was a time of high ophidian diversity across much of the world, dominated by booid-grade snakes. A series of extinction events during and at the end of the Eocene resulted in a depauperate fauna of mainly small snakes in Europe and North America, and the disappearance of several lineages. Due to a poor Eocene fossil record, it is not yet known whether similar extinction events occurred in Afro-Arabia, but later fossils suggest that African snake faunas evolved differently from those in Europe. Here we report the first well-known Eocene snake fauna from Africa, derived from the Priabonian-aged locality BQ-2 in the Fayum region of northern Egypt. The fauna is diverse, consisting of seven species, including the previously known madtsoiid Gigantophis garstini and the palaeophiid Pterosphenus schweinfurthi. Additional species include two booids, a tropidophiid, a probable russellophiid, and a new colubroid, Renenutet enmerwer, gen. et sp. nov. The fauna in many respects presents a typical Eocene character, dominated by booid species and Pterosphenus, and including a madtsoiid. However, it is atypical in the relative importance of the colubroid R. enmerwer, consisting of ∼15% of the total number of specimens. Also unexpected is the tropidophiid, today restricted to the neotropics; however, it provides a possible connection between the extant range and European fossils referred to Tropidophiidae. The description of this fauna provides initial context for further study of the evolution of snakes in Africa, particularly with respect to changes through the Eocene and beginning of the Oligocene.