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Dryolestoids are an extinct mammalian group belonging to the lineage leading to modern marsupials and placentals^,. Dryolestoids are known by teeth and jaws from the Jurassic period of North America and Europe^,, but they thrived in South America up to the end of the Mesozoic era and survived to the beginnings of the Cenozoic^,,,,. Isolated teeth and jaws from the latest Cretaceous of South America provide mounting evidence that, at least in western Gondwana, dryolestoids developed into strongly endemic groups by the Late Cretaceous^,,,,,. However, the lack of pre-Late Cretaceous dryolestoid remains made study of their origin and early diversification intractable. Here we describe the first mammalian remains from the early Late Cretaceous of South America, including two partial skulls and jaws of a derived dryolestoid showing dental and cranial features unknown among any other group of Mesozoic mammals …