In 1889, Florentino Ameghino erected Patriarchus palmidens, based on a specimen from a western outcrop of the Santa Cruz Formation (early Miocene) and associated it with the ‘Notohippidian stage’. Later, Ameghino added seven other species to the genus from eastern localities of the same formation. Since 1900, Patriarchus has been considered to be a junior synonym of Protypotherium. Here, we present a systematic revision and recognize the genus Patriarchus as monospecific, with Pa. palmidens characterized by i1–c mesiodistally expanded, labially convex, and similar in size; i1–c with a short lingual sulcus that does not extend to the base of the teeth and ‘V’-shaped in occlusal view; p1 labially and lingually bilobate, with trigonid larger than talonid; and i1–p1 in a continuous series without overlapping. Five of the remaining species are recognized as belonging to Protypotherium. Therefore, Patriarchus is presently monospecific (Pa. palmidens) and restricted to the western region of Santa Cruz Province, particularly to the Río Bote locality. Patriarchus is included for the first time in a cladistic analysis to discover its phylogenetic relationships within the Interatheriidae. It is nested within the most derived Interatheriinae and is recovered as the sister group of the Laventan Miocochilius; this clade is, in turn, the sister group of Cochilius plus Interatherium. These results support the hypothesis that the origin of the Miocene Interatheriines was a single evolutionary event.