Rodentia is a species-rich group with diversified modes of life and diets. Although rodent skull morphology has been the focus of a voluminous literature, the functional significance of its variations has yet to be explored in live animals. Myomorphous rodents, including murids, have been suggested to represent “high-performance generalists.” We measured in vivo bite force in 14 species of wild and lab-reared murid rodents of various sizes and diets to investigate potential morphofunctional differences between them. We dissected their skulls and computed a biomechanical model to estimate bite force. We first tested if our model allowed good estimation of in vivo data. Then, using morphological, in vivo and estimated bite force data in a phylogenetic context, we aimed to find the drivers of bite force differences among species. Estimated and in vivo bite forces were strongly correlated, which indicates that (a) biomechanical models allow a good estimation of real performance, and that (b) size and muscular changes (increased mass, fiber length, and PCSA) are the main drivers of bite performance differences. Myomorphous rodents, therefore, may have evolved high bite force through a combination of changes in size and musculature, which gave them a great versatility in their ability to process food. We found mixed results at the intraspecific level, with only some species displaying a good fit between estimated and in vivo measurements. We suggest that limited variation in size and muscular organization, and increased behavioral variation might decrease the precision of bite force estimates within species.