Aim: Tropical South America, in particular Amazonia, has been identified as the area of the basal diversification of several large mammal clades. Whether this scenario also holds for younger and widely distributed clades remains unclear. Here, we assessed the historical biogeography of a young but diverse and widely distributed mammal clade. Location: The Neotropics. Taxon: Long-tailed mice of the genus Oligoryzomys. Methods: We estimated a dated species tree by sampling five genes (one mitochondrial and four nuclear) from 30 of the 32 living species of the genus. We inferred the distribution of the most recent common ancestors (MRCAs) of distinct species groups, using a 13 ecoregion scheme and fitting three biogeographical models, to simulate dispersal events under the selected model. Results: The DEC model best explained the diversification of Oligoryzomys. The MRCA of the genus had an age of ~2.64 Mya and its ancestral area was inferred as a large region encompassing Boreal and Southern Amazonia, Chaco and Tropical Andes. Subsequent vicariance events, followed by dispersal events towards the present, account for its diversification and wide distribution. Main conclusion: The biogeographical history of Oligoryzomys is complex. It originated in the northern half of South America; and then after a series of vicariant events, a series of dispersion events allowed it to colonize southern South America, the Andes and closer to the present Central and North America. This radiation, which constitutes one of the fastest and largest Pleistocene diversifications of Neotropical mammals, involves events previously suggested for other groups (e.g. Andean diversification), others that are novel for rodents and for the most part for South American mammals (e.g. the identification of the Chaco as a centre of diversification).