A new mammal, Henosferus molus, n.gen. and n.sp., from the Callovian–Oxfordian (latest Middle to earliest Late Jurassic) Cañadón Asfalto Formation from Chubut Province (Argentina) is described. This taxon corresponds to a new species clearly different from Asfaltomylos patagonicus from the same locality and stratigraphic level. This new species is based on three lower jaws with relatively well-preserved dentition. The lower jaw shows a primitive morphology having a Meckelian groove, a prominent medial flange associated with a lateral ridge of the dentary, and a deep dentary trough, which possibly indicates the presence, even though reduced, of postdentary bones still attached to the dentary. The lower dental formula is i4, c1, p5, m3. The premolars are simple, bearing a main cusp, while the molars appear to be tribosphenic, with an obtuse to right-angled trigonid and a basined talonid with three cusps. This association of plesiomorphic features in the jaw and derived features in the molars is documented in several taxa of the recently proposed Australosphenida. A phylogenetic analysis of mammaliaforms nests the new species with Asfaltomylos from the same locality and stratigraphic level; Henosferidae, new family, is recognized for Asfaltomylos and Henosferus, representing the basal radiation of Australosphenida. Henosferidae is the sister group to Ambondro from the Middle Jurassic of Madagascar, which, in agreement with previous phylogenies, is the sister taxon to the remaining australosphenidans. Additionally, our phylogenetic analysis does not support the inclusion of australosphenidans within eutherians. Henosferids likely retained some connection of the postdentary elements with the dentary; therefore, if the inclusion of Monotremata within Australosphenida is confirmed, final freeing of the postdentary elements and development of a tri-ossicular middle ear would be convergent events in Monotremata and Theria. Finally, the distinctiveness of the yet sparse South American record of Jurassic mammals when compared with the slightly better documented Cretaceous data is emphasized. The clear faunistic break between the Middle Jurassic and Early/Late Cretaceous underlies our rudimentary understanding of the evolution of Mesozoic mammals in Gondwana.