It is named for the historic Matapeake tribe, who lived there at the time of English colonization in 1631. Their chief village was on the southeast side of the island. They were an Algonquian-speaking tribe, related to the paramount chiefdom of the Nanticoke.
Before construction of the Chesapeake Bay Bridge, Matapeake was the eastern terminus of a cross-bay ferry. The ferry building is part of the Matapeake Maritime Center.