Mansonella streptocerca is a species of neglected skin-dwelling filarial nematode parasite with scarce epidemiologic data from Central Africa. We conducted a cross-sectional survey of 1,007 adults from 51 rural and semiurban communities in Gabon to update prevalence estimates and identify risk factors. Molecular analyses by quantitative PCR detected filarial DNA in 18.3% of skin snips; M. streptocerca predominated (14.2%), and Onchocerca volvulus (3.4%) occurred focally in a single rural area. Blood-dwelling parasite species such as Loa loa, M. perstans, and Mansonella sp. "DEUX" were rarely detected. M. streptocerca infection was 4 times more frequent in rural areas than in semiurban areas and independently associated with male sex, urticaria, and poor housing conditions. Wolbachia DNA occurred in 28% of M. streptocerca-positive samples, suggesting endosymbiosis. Our findings reveal a substantial but overlooked burden of M. streptocerca nematodes in Gabon and emphasize the need for integrated surveillance of skin-dwelling filarial infections in Central Africa.