Pyozia mesenensis, gen et sp. nov. is the second varanopid synapsid from the Middle Permian Krasnoschelsk Formation of Russia. Pyozia is a basal varanopid similar to Archaeovenator in having teeth that lack lateral compression or serration, lacking a caniniform tooth or region on the maxilla, and possessing four premaxillary teeth. Pyozia uniquely possesses a medial contact of the maxilla with the quadratojugal with no lateral exposure allowing the jugal to form part of the skull's ventral margin, and rounded interpterygoid vacuities just anterior to the basipterygoid articulations. Phylogenetic analysis places Pyozia as sister taxon to the terminal dichotomy of Mycterosaurinae and Varanodontinae. The newly described Upper Carboniferous Archaeovenator is again found to be the most basal varanopid.The Permian saw a large-scale changeover of the synapsid fauna, with derived, but ecologically similar, taxa, replacing more primitive “pelycosaurs.” Leaf-shaped tooth-bearing caseids were replaced in the Middle and Late Permian by herbivorous pareiasaurs with similar dentition, and Edaphosaurus was replaced by therapsids capable of processing plant material. The large predators of Sphenacodontidae were similarly replaced by therapsid predators. The small to medium sized predator niche, however, was continuously occupied by varanopids. The discovery of the basal Pyozia suggests that varanopids maintained their diversity in the Middle Permian.