The Middle Permian tetrapod fauna of the South African Beaufort Group is taxonomically diverse and includes representatives of all major therapsid groups, including the earliest records of Eutheriodontia. In the Middle Permian, eutheriodonts are represented mainly by large therocephalians, which made up a large proportion of the vertebrate predators in these faunas. Here we describe the skull and partial skeleton of a large therocephalian from the uppermost Tapinocephalus Assemblage Zone (AZ) of South Africa. A combination of features, including the short snout, presence of three to four upper postcanines and presence of teeth on the pterygoid processes, indicates that the new specimen belongs to the earliest-diverging therocephalian family, Lycosuchidae. The presence of a well-developed midline ridge on the ventral surface of the vomer indicates that the new specimen can be referred to Simorhinella baini, a species previously represented only by a tiny juvenile skull. The new specimen forms the basis for a taxonomic re-evaluation of the Lycosuchidae as well as of the geographic and stratigraphic range of the family. We recognize two valid species within the Lycosuchidae: the type species Lycosuchus vanderrieti represented by five specimens and Simorhinella baini represented by two specimens, with an additional 22 specimens currently identifiable as Lycosuchidae incertae sedis. Lycosuchid specimens range throughout the Tapinocephalus and Pristerognathus AZs; specimens of Simorhinella are restricted to the Tapinocephalus AZ, whereas Lycosuchus specimens are documented in both the Tapinocephalus and Pristerognathus AZs.