Monodelphis (short-tailed opossums) is the most diverse genus in the family Didelphidae, including at least 20 recognized species. This paper describes a new species of short-tailed opossum from the lowland forests of Loreto, northeastern Peru. The new species is intermediate in size and coloration between M. ronaldi, a species recently described on the basis of 1 specimen from southeastern Peru, and M. adusta, a more common species distributed across western Amazonia. However, the new species is sympatric only with M. emiliae. Diagnostic characters include overall large size, conspicuously wide buffy stripe on the venter, wide rostrum, narrow postorbital constriction, rounded posterior border of the infraorbital foramen, small and well-separated tympanic processes of alisphenoid, conspicuous posttympanic processes, enlarged canines, small 1st upper premolars, and enlarged cingula on premolars and molars. Whereas morphologically the new species closely resembles M. ronaldi and M. adusta, a phylogenetic analysis of mitochondrial DNA sequences (which did not include M. ronaldi) indicates M. osgoodi as its sister taxon. Examination of molecular data also indicates that M. adusta is paraphyletic relative to M. osgoodi and the new species, and that populations currently referred to M. a. adusta and to M. a. peruviana each represent 2 distantly related and clearly distinct species.