Anopheles coluzzii is a major malaria vector throughout its distribution in west-central Africa. Here we present a whole-genome resequencing study of 77 specimens from eight localities, that covers a large part of this species’ range, including three islands in the Gulf of Guinea: Bioko, São Tomé and Príncipe. Population genomic analyses encompassed structure of mainland populations, of island populations and connectivity between island and mainland populations. Three genetic clusters were found among mainland populations and genetic distances among all populations fit an isolation-by-distance model. Genomic analyses were applied to estimating the demographic history and ancestry (cross-coalescence) for each island. Taken together with the unique biogeography and history of human occupation for each island they present a coherent explanation underlying contemporary levels of genetic isolation between mainland and island populations and among island populations. We discuss the relation of our findings to the suitability of São Tomé and Príncipe islands as candidate sites for potential field trials of genetic-based malaria control strategies.