Determining the incidence and causes of craniodental damage in wild carnivores is often constrained by limited access to specimens with associated ecological data, such as prey type and abundance. We assessed dental condition and cranial injuries in lion, leopard, and spotted hyena in relation to prey and predator populations in Zambia’s Luangwa Valley, where large prey are more abundant and lion and leopard more numerous, and the Greater Kafue Ecosystem, where smaller prey species are more prevalent and lion and leopard less common. In Luangwa, lions had significantly higher rates of tooth fracture, and blunt trauma injuries attributable to prey-handling, compared to Kafue lions. In contrast, leopards in both regions had similar rates of tooth wear and breakage. Overall, lions showed a significantly higher tooth fracture rate than leopards on a per tooth basis. Spotted hyenas had the highest rates of tooth wear and fracture among all three carnivores, and greatly exceeded previously recorded rates based on historical samples. Despite larger numbers of lion and leopard in Luangwa, there was no difference in incidence of intraspecific injuries between regions. These results are consistent with a greater abundance of large prey species, especially buffalo, in the diets of Luangwa lions, and previous work showing a reliance on smaller prey species in Kafue throughout the large carnivore guild.