Large carnivores play a crucial role in their native ecosystems, but their populations are rapidly declining across the African continent. West Africa is no exception, with large protected areas often forming the last strongholds for these species. Little is known about the population status and ecology of large carnivores in the region, hampering the design and implementation of effective conservation strategies. We conducted a camera-trap survey during the dry season in Niokolo-Koba National Park, the largest terrestrial protected area in Senegal and the second largest in West Africa, to investigate the spatio-temporal ecology of the four large carnivores inhabiting the Park: the spotted hyaena Crocuta crocuta, leopard Panthera pardus, West African lion Panthera leo leo and African wild dog Lycaon pictus. Spotted hyaenas and leopards had the widest spatial distribution and highest probability of site use. Spotted hyaena site use was positively associated with leopard relative abundance index and negatively associated with normalized difference vegetation index, whereas only distance to the nearest road influenced leopard site use. Distance to the Gambian River was the most important covariate positively affecting site use by lions. African wild dog site use was negatively associated with the relative abundance indices of lions and leopards. Lions, spotted hyaenas and leopards showed strong overlap in their activity patterns. By providing new information on the ecology of large carnivores in West Africa, including where they range and which habitats are critical for their survival, our study will facilitate conservation planning. Our findings lay the foundations for future research to conserve these threatened species in West Africa effectively and to guide ranger patrol efforts, which are key for their long-term survival.