Mammals have adapted to different habitats, food types, and modes of locomotion, which are reflected in a diverse range of paw morphologies. While the behavior of rats and guinea pigs is well defined, especially in terms of their locomotor and foraging behaviors, the anatomy of their foot pads has not yet been explored and compared. This study investigated adaptations in paw morphology in the domestic guinea pig (Cavia porcellus) and the brown rat (Rattus norvegicus). We predicted that rat paws would display adaptations associated with paw dexterity for handling prey items and climbing, whereas guinea pig paws would support mechanical pressure absorption for a herbivorous, sedentary, and terrestrial lifestyle. Using histology techniques and scanning electron microscope, we show that rat paws have many small, deformable pads that are relatively spaced out to enable movement. The pads are clustered toward the anterior of the foot, which coincides with where the most force occurs during locomotion, as rats walk on their toes and toward the front of their paw. Guinea pigs had fewer and larger pads and the posterior pad of the forepaw was textured and contained cartilage, which may act to reduce friction and compression during standing and locomotion. We suggest that differences in paw morphology in rat and guinea pig are associated with loading during locomotion as well as paw mobility. Examining paw morphology and movement abilities in more species will give further insights in to the evolution of locomotor adaptations and paw dexterity in rodents. Anat Rec, 302:2300–2310, 2019. © 2019 American Association for Anatomy