Akodon is the second most diverse genus of sigmodontine rodents, comprising 40 extant species. Widely distributed through different environments of South America, the genus ranges from forested to open-vegetation areas, from semiarid to mesic regions, and from Andean altitudes to the lowlands of eastern Brazil. In Brazil, most species are from the Atlantic Forest, inhabiting lowland and montane habitats, with a few taxa also present in areas transitional with the Cerrado and Pantanal. Based on an integrative approach of genetics (cytogenetic and molecular data) and morphology (qualitative and quantitative external and craniodental data), we present in this contribution the hypothesis of a new species of Akodon based on specimens collected in the southwestern limit of the Cerrado domain, in the seasonally dry forests of the Serra da Bodoquena, Mato Grosso do Sul, Brazil. The new species was recovered as a distinct lineage sister to Akodon philipmyersi, a poorly known species from the Northern Campos grasslands of Misiones Province, Argentina, and can be distinguished from its congeners by its karyotype (2n = 40, FN = 40), morphology (morphometric, pelage, and skull characters), as well as by its degree of genetic divergence (above 7.5% in Cytb sequences). This new species is endemic to the Cerrado, one of the world's biodiversity hotspots, and to Serra da Bodoquena, one of the top priority areas for conservation in Brazil. Moreover, the new species increases the number of lineages of Akodon in Brazil, emphasizing the richness and endemism currently found in the Cerrado domain, and the importance of the open formations to the diversification of Neotropical taxa.