We describe a new species of the didelphid marsupial genus Monodelphis from Brazil, where it appears to be widely distributed in the states of Pará, Mato Grosso, Rondônia, and Acre. Monodelphis saci, new species, belongs to the subgenus Mygalodelphys, and analyses of DNA sequence data suggest that it is most closely related to M. handleyi, M. osgoodi, and M. peruviana. Diagnostic morphological traits include pelage coloration, qualitative aspects of craniodental morphology, and a distinctive range of morphometric variation. The new species has sometimes been misidentified in the literature as M. kunsi, a distinct but apparently allopatric taxon. Monodelphis saci occurs sympatrically with M. emiliae, M. glirina, and M. touan in the rainforested lowlands south of the Amazon River.