Habitat loss and fragmentation, hunting pressure, and human–wildlife conflict threaten the survival of primates across Africa. Particularly dramatic forest losses have occurred outside protected areas in the Guinean forest–savannah transition zone. Using the Boé region, Guinea-Bissau, as a case study, we investigated whether and how this rapidly humanized mosaic of wooded savannah, gallery forests and cropland could sustain viable primate populations. We conducted line transect surveys and reconnaissance (recce) walks to assess populations of one Critically Endangered (chimpanzee Pan troglodytes verus), one Endangered (Temminck's red colobus Piliocolobus badius temminckii), one Vulnerable (king colobus Colobus polykomos), and one Near Threatened (sooty mangabey Cercocebus atys) arboreal primates across a 104 km2 section of Boé in the dry season of 2016. Using the standing crop nest count method we estimated a relatively high chimpanzee density (0.77 individuals per km2, 95% CI 0.45–1.34). An assessment of habitat selection showed that chimpanzees prefer semi-dense forest and fallow fields with remnant old trees for nesting, and locations close to rivers. The other primates studied occurred in extremely low densities and were largely restricted to gallery forests. Our results indicate a need for immediate action to ensure the long-term survival of the primate community in the human-dominated landscape of Boé. Our recommendations include action to maintain hunting pressure at a low level, restoring and protecting gallery forests, introducing incentives for farmers for forest protection and primate-friendly practices, and extending the conservation programme to all arboreal primates in the region.