Teeth of omnivores face a formidable evolutionary challenge: how to protect against fracture and abrasive wear caused by the wide variety of foods they process. It is hypothesized that this challenge is met in part by adaptations in enamel microstructure. The low-crowned teeth of humans and some other omnivorous mammals exhibit multiple fissures running longitudinally along the outer enamel walls, yet remain intact. It is proposed that inter-prism weakness and enamel property gradation act together to avert entry of these fissures into vulnerable inner tooth regions and, at the same time, confer wear resistance at the occlusal surface. A simple indentation experiment is employed to quantify crack paths and energetics in human enamel, and an extended-finite-element model to evaluate longitudinal crack growth histories. Consideration is given as to how tooth microstructure may have played a vital role in human evolution, and by extension to other omnivorous mammals.