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Wildlife conservation in the Anthropocene means there is a pressing need to find ways for wildlife and humans to share landscapes. However, this is challenging due to the complex interactions that occur within social-ecological systems (SES). This challenge is exemplified by grey wolf management in the American West, where human governance systems influence where and at what densities carnivores persist, thereby regulating and limiting the impacts of carnivores on both human and ecological communities. Here, we build a SES conceptual framework to disentangle the interdependencies between wolves and humans, including the ecological impacts of wolves and people in anthropogenic landscapes and the socio-economic forces shaping human–wolf interactions now and in the future. A key lesson is that coexistence rests not only on the biophysical capacity of a landscape to be shared by humans and wolves, but also on the capacity for human societies to adjust to and accept some level of conflict with wolves. As such, a holistic view that recognizes humans, our social systems and institutions as key actors and attributes of ecological systems can advance the theory and practice of coexistence.