Abstract A Zika virus seroepidemiology study was performed in 1084 blood donors collected from August to October 2015 in six sites of Cameroon representing a large panel of eco-environments. Samples were tested using an anti-NS1 IgG ELISA detection kit and positives were further confirmed by seroneutralization. The observed global seroprevalence was low (around 5%, peaking at 10% and 7.7% in Douala and Bertoua, respectively) with risk factors associated with seropositivity pointing to the existence of a local (peri-)sylvatic cycle of transmission. These results call attention to the potential introduction and subsequent spread in African urban areas of Asian genotype Zika virus currently circulating in the Americas and adapted to transmission by peri-domestic mosquitoes. They should leverage reinforced surveillance efforts in Africa.