The habitat of Onchocerca volvulus is the body of its host. In the blackfly, microfilariae reside in the thoracic flight muscles. In humans, microfilariae can be found in the skin, lymph vessels, lymph nodes, blood, urine, cerebrospinal fluid, and internal organs (especially the eyes). Adults can be found knotted together in pairs or groups in the subcutaneous tissues. Due to host immunological reactions, these groups of worms often become encapsulated in fibrous tissue mainly composed of collagen. When these sites are located over bones such as a joint or skull, a conspicuous nodule called an onchocercoma appears, which is generally about 3 cm in diameter. Nodule location depends on geographical area, with most infections in Africa exhibiting nodules below the waist (especially on the knees and pelvic area), and those in Central America exhibiting nodules above the waist (especially on the neck and head). This relationship is based on the biting preferences of the blackfly vector, with African flies preferring to bite below the waist, and Central American flies preferring to bite above the waist.

Onchocerca volvulus will generally be found causing disease in savanna and rain forest areas, although occasionally it can be found in arid savannas and desert areas as well.

Habitat Regions: tropical ; terrestrial

Terrestrial Biomes: desert or dune ; savanna or grassland ; forest ; rainforest ; scrub forest

Aquatic Biomes: rivers and streams

Wetlands: marsh ; swamp

Other Habitat Features: riparian