Tooth enamel is inherently weak, with fracture toughness comparable with glass, yet it is remarkably resilient, surviving millions of functional contacts over a lifetime. We propose a microstructural mechanism of damage resistance, based on observations from ex situ loading of human and sea otter molars (teeth with strikingly similar structural features). Section views of the enamel implicate tufts, hypomineralized crack-like defects at the enamel–dentin junction, as primary fracture sources. We report a stabilization in the evolution of these defects, by “stress shielding” from neighbors, by inhibition of ensuing crack extension from prism interweaving (decussation), and by self-healing. These factors, coupled with the capacity of the tooth configuration to limit the generation of tensile stresses in largely compressive biting, explain how teeth may absorb considerable damage over time without catastrophic failure, an outcome with strong implications concerning the adaptation of animal species to diet.