Astrapotherium is the best-known member of the placental order Astrapotheria. This large herbivore inhabited the Patagonian ecosystems during early and middle Miocene times. The genus is widely represented in the early Miocene Santa Cruz Formation, with a dozen nominal species, of which Astrapotherium magnum and Astrapotherium burmeisteri are the only ones herein considered as valid. The middle Miocene record was limited to few fragmentary remains from the Río Frías Formation and presumably from the Collón Cura Formation, described as Astrapotherium hesperinum, a species name here interpreted as nomen vanum. Here we describe an almost complete skull with associated mandible derived from the Collón Cura Formation in the vicinities of Comallo, in Río Negro Province (Argentina). It is by far the most complete astrapothere material from middle Miocene rocks of high latitudes, and it is referred to Astrapotherium guillei sp. nov. It differs from the remaining species essentially in lacking P3, achieved convergently with the latest diverging uruguaytheriines. The astrapotheriines diversified in high latitudes during the early Miocene, but they retained a stereotyped morphotype and became progressively less diverse, unlike their Northern counterparts (the Uruguaytheriinae). Astrapotherium guillei is the latest known Patagonian astrapothere and represents the final expression of the Astrapotheriinae's decline thus far.