A new genus and species of Toxodontidae from the Huayquerian (late Miocene) of El Cajón Valley (Catamarca, Argentina) is described. Calchaquitherium mixtum gen. et sp. nov. (Toxodontinae) is characterized by a combination of features of different genera, being closest to Mixotoxodon, Xotodon, and Nonotherium. Cladistic analysis of the family Toxodontidae has been attempted in order to assess the phylogenetic relationships of the new taxon. Four genera of the families Leontiniidae and Notohippidae were used as outgroups. The five subfamilies previously included in Toxodontidae do not represent monophyletic groups according to this analysis. A new classification of Toxodontidae, with two subfamilies, Nesodontinae and Toxodontinae, with three main groups of genera within the latter, is proposed.