Among the archaic ‘ungulates,’ pleuraspidotheriids are well documented by skulls and postcranial elements of Pleuraspidotherium from Berru and Cernay-lès-Reims (late Paleocene, Paris Basin, France). Nevertheless, the relationships of pleuraspidotheriids (i.e., Pleuraspidotherium, Orthaspidotherium, and Hilalia) to other ‘condylarths’ have not been conclusively settled. They have been related to the typically North American Meniscotheriidae, Phenacodontidae, and Mioclaenidae, and even to the modern ungulates Perissodactyla and Artiodactyla. We here provide additional data, especially from the first complete skull of Orthaspidotherium, and highlight a mosaic of plesiomorphic and derived characters that distinguish Pleuraspidotheriidae from all other ‘ungulates.’ Their basicranial morphology approximates the ancestral morphotype of artiodactyls, but this results from symplesiomorphies. Pleuraspidotheriids exhibit the following synapomorphies: strong processes on the petrosal and enclosure of the facial nerve by the tympanic process and tympanohyal. Although their dentition resembles that of perissodactyls, meniscotheriids, and phenacodontids, the development of a pseudohypocone from the metaconule unambiguously shows that these similarities arose by convergence. Other evolutionary tendencies are the strong reduction of the hypoconulid, molarization of last premolars, development of lingual cingulum on M2, lengthening of the snout, and presence of diastemata. The pleuraspidotheriid tarsal morphology is primitive and not uncommon among ‘condylarths’ but presents some synapomorphies such as a calcaneum with a transverse cuboid facet and an astragalus with a squatting facet, cotylar fossa, and sustentacular hinge. Our study does not indicate a close relationship of Pleuraspidotheriidae with any of the archaic or modern ‘ungulates’ mentioned above. Instead, primitive arctocyonids could represent a possible ancestral morphotype for pleuraspidotheriids.