Understanding the interactions between local people and chimpanzees is crucial to develop sustainable wildlife conservation strategies and management policy in the Mbam-Djerem National Park (MDNP). The MDNP covers about 416,512 ha and shelters the Nigeria-Cameroon chimpanzee (Pan troglodytes ellioti) being the most endangered of all currently recognized chimpanzee subspecies. Close to 30,000 people live in the periphery of the MDNP and depend on the park’s resources for subsistence. We investigated the extent of, and factors leading to, the interactions between people and chimpanzees through a socio-economic survey focusing on households (124) and individual interviews (38) in 30% of villages around MDNP. About 95% of the respondents stated that human–wildlife conflict is an issue around MDNP. Access to resources (78.9%), crop damage (84%), and animal attack (11.3%) were the main sources of conflicts. The ground squirrel Xerus erythropus (59.7%), the green monkey Chlorocebus aethiops (20.2%), chimpanzees (7.3%) and baboons Papio anubis (5.6%) were identified as the main conflict animals and the destroyed crops included peanuts (70.2%), maize (15%) and cassava (5%). The population perceptions differed between the park’s four sectors and were significantly influenced by education and the main livelihood activity. The study also provided quantitative evidence on the role of personal and religious beliefs on the behavior towards chimpanzees. Our findings suggest that the improvement of income-generating activities and education will contribute to strengthening the conservation of chimpanzees.