The Eocene was a key interval for the diversification of squamates worldwide. However, little is known about their early evolution in Africa due to the scarcity of Paleogene fossil squamates from that continent. One of the most important Eocene vertebrate assemblages in Africa is known from the Fayum Depression of Egypt, but only a few lizards and snakes have been reported from these deposits. Here we report the first Paleogene record of the clade Amphisbaenia in Egypt, from the lowest upper Eocene Birket Qarun Locality 2 (BQ-2). It corresponds to a mid-trunk vertebra characterized by a depressed centrum with a flattened base, hemispherical synapophyses, and absence of a neural spine. Additional material from BQ-2 includes seven vertebrae attributed to colubroidean snakes. One trunk vertebra resembles those of early Eocene Procerophis from India while the remaining colubroidean vertebrae are referred to Renenutet enmerwer. Caudal vertebrae of Renenutet are described here for the first time. Similarities in the caudal vertebral morphology between BQ-2 Renenutet and Thaumastophis missiaeni from the lower Eocene of India reinforce the hypothesis of a close affinity between them. The presence of cf. Procerophis and Renenutet in Egypt adds to the evidence for terrestrial faunal exchange between Asia and northern Africa during the early/middle Eocene along the southern margin of the Tethyan Sea.