Because it can lead to retaliatory killing, livestock depredation by large carnivores is among the foremost threats to carnivore conservation, and it severely impacts human well-being worldwide. Ongoing climate change can amplify these human-wildlife conflicts, but such issues are largely unexplored, though are becoming increasingly recognized. Here, we assessed how the availability of primary resources and wild prey interact to shape large carnivore selection for livestock rather than wild prey (i.e., via prey switching or apparent competition). Specifically, we combined remotely sensed estimates of primary resources (i.e., water availability and primary productivity), wild prey movement, and 7 years (2015-2021) of reports for livestock depredation by African lions (Panthera leo) in the Makgadikgadi Pans ecosystem, Botswana. Although livestock depredation did not vary between wet versus dry seasons, analyses at finer temporal scales revealed higher incidences of livestock depredation when primary production, water availability, and wild prey availability were lower, though the effects of wild prey availability were mediated by water availability. Increased precipitation also amplified livestock depredation events despite having no influence on wild prey availability. Our results suggest that livestock depredation is influenced by the diverse responses of livestock, wild prey, and lions to primary resource availability, a driver that is largely overlooked or oversimplified in studies of human-carnivore conflict. Our findings provide insight into tailoring potential conflict mitigation strategies to fine-scale changes in resource conditions to efficiently reduce conflict and support human livelihoods.