The medial Permian (similar to 270-260 Ma: Guadalupian) was a time of important tetrapod faunal changes, in particular reflecting a turnover from pelycosaurian- to therapsid-grade synapsids. Until now, most knowledge on tetrapod distribution during the medial Permian has come from fossils found in the South African Karoo and the Russian Platform, whereas other areas of Pangaea are still poorly known. We present evidence for the presence of a terrestrial carnivorous vertebrate from the Middle Permian of South America based on a complete skull. Pampaphoneus biccai gen. et sp. nov. was a dinocephalian "mammal-like reptile" member of the Anteosauridae, an early therapsid predator clade known only from the Middle Permian of Russia, Kazakhstan, China, and South Africa. The genus is characterized, among other features, by postorbital bosses, short, bulbous postcanines, and strongly recurved canines. Phylogenetic analysis indicates that the Brazilian dinocephalian occupies a middle position within the Anteosauridae, reinforcing the model of a global distribution for therapsids as early as the Guadalupian. The close phylogenetic relationship of the Brazilian species to dinocephalians from South Africa and the Russian Platform suggests a closer faunistic relationship between South America and eastern Europe than previously thought, lending support to a Pangaea B-type continental reconstruction.