The South American hystricognath rodents are one of the most diverse mammalian clades considering their occupied habitats, locomotor modes and body sizes. This might have been partly evolved by diversification of their masticatory apparatus' structure and its ecological commitment, for example, chisel-tooth digging. In this phylogeny-based comparative study, we test the relationship between ecological behavior and mechanical features of their incisors and molariforms. In 33 species of nine families of caviomorph rodents, we analyze incisor attributes related to structural stress resistance and molar features related with grinding capacity, for example, second moment of inertia and enamel index (EI) (enamel band length/occlusal surface area), respectively. Most of these variables scaled isometrically to body mass, with a strong phylogenetic effect. A principal component analysis discrimination on the EI clustered the species according to their geographic distribution. We presume that selective pressures in Andean-Patagonian regions, on particular feeding habits and chisel-tooth digging behaviors, have modeled the morphological characteristics of the teeth. Subterranean/burrower ctenomyids, coruros, and plains viscachas showed the highest bending/torsion strength and anchorage values for incisors; a simplified enamel pattern in molariforms would be associated with a better grinding of the more abrasive vegetation present in more open and drier biomes.