The Cura-Mallin Formation consists of a series of upper Oligocene to Upper Miocene volcanic and sedimentary rocks deposited in continental settings that crop out in the Andean Cordillera in Chile and Argentina between similar to 37 degrees and 39 degrees S. Since the 1990s few fossil mammals have been recovered from this unit in the surroundings of Lonquimay, south-central Chile (38.5 degrees S), and all of them were assigned to the Early Miocene. After a reassessment of the taxonomic affinities of the fauna so far recovered from the Cura-Mallfn Formation in the Lonquimay area, and based on the radioisotopic ages of the fossil-bearing localities, here we recognized two chronological distinctive mammalian assemblages: one of Early Miocene age (probably Colhuehuapian-Santacrucian SALMA), which includes Nesodon imbricatus and Parastrapotherium sp.; and a second one of late Middle Miocene age (12.8-11.6 Ma; Serravallian; Mayoan SALMA), which includes glyptodonts (Glyptodontidae indeterminate), armadillos (Eutatini indeterminate), macraucheniids (Theosodon sp.), a new interatheriid species (Protypotherium concepcionensis sp. nov.), and a likely platyrrhine monkey. Therefore, in contrast with previous interpretations, the fauna from Lonquimay is not uniquely restricted to the Early Miocene. The fossil mammals and plants recognized from the area indicate the persistence of mostly temperate and forested habitats with permanent bodies of water during the Early to latest Middle Miocene. This suggests that this part of the Andean Cordillera (38 degrees-39 degrees S) did not reach enough paleoaltitudes ( > 1000 m) to cause an important orographic rain shadow effect in the foreland basins at least after the late Middle Miocene (c. 12 Ma). However, the role of Neogene South Hemisphere climatic changes in triggering, or reinforcing, the foreland desertification along the south-central Andes is an additional factor that cannot be discarded.