Relationships between primates and snakes are of widespread interest from anthropological, psychological, and evolutionary perspectives, but surprisingly, little is known about the dangers that serpents have posed to people with prehistoric lifestyles and nonhuman primates. Here, we report ethnographic observations of 120 Philippine Agta Negritos when they were still preliterate hunter-gatherers, among whom 26% of adult males had survived predation attempts by reticulated pythons. Six fatal attacks occurred between 1934 and 1973. Agta ate pythons as well as deer, wild pigs, and monkeys, which are also eaten by pythons, and therefore, the two species were reciprocally prey, predators, and potential competitors. Natural history data document snake predation on tree shrews and 26 species of nonhuman primates as well as many species of primates approaching, mobbing, killing, and sometimes eating snakes. These findings, interpreted within the context of snake and primate phylogenies, corroborate the hypothesis that complex ecological interactions have long characterized our shared evolutionary history.