The field of human-animal interactions (HAI) is focused primarily on human-companion animal relationships, especially the impact of such relationships on human health. Here, we demonstrate how a wider, integrative approach, consisting of an evolutionary framework, provides new insights into the varieties of HAIs and their emergence and significance during human evolution. Along with other HAI researchers, we show that those HAIs which develop into interrelationships can best be treated as ecological symbioses that involve fitness interdependence among the symbionts and entail the evolution of phenotypic traits that support the adaptive features of the symbionts. We present the novel idea that the formation of mutualistic symbiotic relationships through the process of domestication depended on the prior evolution of hominin hypersociality and ultrasociality in modern humans. Hypersociality was characterized by high levels of social cooperation and social tolerance that became increasingly important for human social life and cooperative hunting. The further development of ultrasociality in modern humans consisted of the development of large-scale (i.e., beyond the hunting band) cooperative social networks of genetically unrelated individuals. This depended on the evolution of further enhancements in socio-cognitive skills, especially representational abilities (e.g., theory of mind), symbolic capacities, and formation of tribal societies with complex social institutions. These modern cognitive and socio-cultural features were made possible by significant brain reorganization during the past 60,000 years. Tribal social institutions were founded on normative moral sentiments and behavior and regulated and ultimately reduced levels of lethal violence. The extension of fitness interdependent, cooperative relationships to large networks of unrelated individuals (i.e., ultrasociality), we argue, was foundational in modern humans to the formation of mutualistic symbioses (i.e., process of domestication) with other animals. Because they are an outgrowth of ultrasociality, we suggest that the term “extended ultrasociality” appropriately describes human interrelationships with domesticated animals. We further suggest that these human-animal interrelationships are unique in that they become imbued with and immersed in our symbolic world, as is demonstrated by the earliest representational art in caves after 50,000 years when enhanced modern human representational and symbolic capacities were evolving. An evolutionary framework invites new questions and avenues for research.