The hypothesis that dangerous snakes served as evolutionary selective pressures on traits characterizing the Order Primates (Snake Detection Hypothesis, SDH), specifically vision and aspects of the brain, has received recent attention. We provide data on 52 encounters between chimpanzees (Pan troglodytes verus) in a savanna landscape and snakes and other large reptiles at the Fongoli site in Senegal, over the course of eight years. These encounters yielded data on 178 interactions between identified individual chimpanzees and reptiles. The majority of encounters with identified reptiles (62%) involved potentially deadly snakes. Constrictors of the family Pythonidae were encountered more frequently than any other reptile. Chimpanzees exhibited a variety of reactions to reptiles, ranging from attacking with objects to ignoring them. Even reptiles other than snakes were met with some degree of alarm when they were in water or moving quickly. We assessed variables that may affect apes’ reactions, as well as the age-sex class of chimpanzees. As a test of Isbell’s snake detection hypothesis, we examined chimpanzees’ reaction intensity to venomous versus constricting snakes but found no difference. We did find significant age-sex differences in chimpanzees’ reactions to snakes, with adolescent males exhibiting higher-intensity reactions than adult males and females and adolescent female chimpanzees. Chimpanzees reacted at significantly higher intensities when snakes were arboreal in location, but reptile species, size, and activity did not significantly influence individuals’ reactions to snakes. We also report one inferred encounter between an adult female chimpanzee and a venomous snake, which led to her death. Our data suggest that snakes are significant threats to chimpanzees in savanna environments and support the hypothesis that danger from snakes could have exerted significant evolutionary pressure on the Order Primates.