The unguis (hoof, claw, or nail) of the first digit (D1, also known as the thumb or pollex) of the tetrapod hand exhibits numerous functional adaptations, but its macroevolutionary association with ecological diversity is unknown. Across Rodentia, we find that most extant genera and ancestral lineages bear D1 nails. Exceptions follow structure-function associations that arose independently multiple times, specifically, the gain of D1 claws with subterranean habits and the loss of D1 ungues with oral-only feeding behavior. We hypothesize that early acquisition of D1 nails and manually dexterous food handling was crucial for rodents to adaptively leverage cranial specializations for efficient gnawing and thereby exploit hard seeds and nuts, a niche that they dominated after the extinction of multituberculates. Our study recasts ideas about rodent evolution and uncovers a previously unrecognized contributor to their successful radiation.