The bivalve Megadesmus is described from the Late Permian Volksrust Shale Formation in the northeastern Karoo Basin, South Africa; this is the first reported discovery of this genus in Africa. The fossil is large, 9 cm dorsally and 8.4 cm laterally, and both valves are articulated indicating minimum transport after death. The bivalve was encased in interbedded siltstone-shale that constitutes the distal sediments of a prograding delta, at the Beaufort Group–Ecca Group boundary. Megadesmus is known from other continents (Australia, India, Siberia, South America and Tasmania) where its presence indicates exclusively marine conditions. The implication for the northeastern Karoo Basin during the Late Permian is that a marine enclave still existed in this geographic area, and that terrestrial conditions did not yet prevail as in the southern basin region.