African wild dogs (Lycaon pictus) are endangered largely because their population-density is low under all conditions. Interspecific competition with larger carnivores may be a factor limiting wild dog density. The density of wild dogs on a 2600-km2 area of the Selous Game Reserve (Tanzania) was 0.04 adults/km2. Spotted hyaena (Crocuta crocuta) density for the same area was estimated by audio playbacks as 0.32 hyaenas/km2. Lion (Panthera leo) density, determined from the ratio of hyaenas to lions, was 0.11 lions/km2. Across six ecosystems including Selous, there were strong negative correlations between wild dog and hyaena densities (r = −0.92; p = 0.01) and between wild dog and lion densities (r = −0.91; p = 0.03). Hyaenas out-numbered wild dogs by ratios ranging from 8:1 to 122:1. Ratios of lions to wild dogs ranged from 3:1 to 21:1. The diets of hyaenas and wild dogs overlap extensively; those of wild dogs and lions show less overlap. Where hyaenas are common and visibility is good, interference competition from hyaenas at wild dog kills is common and reduces wild dogs’ feeding time. Where hyaena density is lower and visibility is poor, interference competition at wild dog kills is rare. Wild dogs are commonly killed by lions and occasionally by hyaenas. These data suggest that competition with spotted hyaenas may limit or exclude wild dogs when hyaena density is high. Competition with lions appears less intense, but direct predation by lions on wild dogs is important. Competition and predation by larger carnivores may be of broad importance to the conservation of wild dogs and other medium-sized carnivores.