The direction of mastication revealed by dental microwear was studied in relation to changes in the structure of the masticatory apparatus in the Issiodoromyinae (Rodentia, Mammalia). Our results offer a rare opportunity to assess the order of establishment of the morphological characters that are related to the acquisition of propalinal mastication in an extinct lineage. Elfomys and Pseudoltinomys show cuspidate tooth crowns, a high mandibular condyle, and a significant lateromedial orientation of the masticatory muscles (superficial masseter and internal pterygoid) in association with oblique chewing movements. In contrast, the Issiodoromys lineage is characterized by a flat molar occlusal surface, a low mandibular condyle, and posterior orientation of the masseter and pterygoid associated with slightly oblique to propalinal chewing. We show that striking convergences with some members of Ctenohystrica have occurred in the evolution of the Issiodoromyinae.