In the mid-sixteenth century, the island was also the site of a Portuguese Jesuit mission. The Muslim states on Ternate and Halmahera resented the outpost for its proselytising activities, and managed to drive the mission from the island in 1571, as a part of a larger Portuguese retreat in the region. In the seventeenth century, Ternate further exerted its power over Morotai by repeatedly forcing major parts of the population to move off the island. Early in the century most of the population was moved to Dodinga, a small town in a strategic spot on Halmahera's west coast. Later, in 1627 and 1628, Sultan Hamzah of Ternate had much of the Christian population of the island moved to Malayu, on Ternate, where they could be more easily controlled.
The island was captured by the Japanese in early 1942. It was taken by American forces in September 1944 during the Battle of Morotai, and used as a staging point for the Allied invasion of the Philippines in early 1945, and of Borneo in May and June of that year. It was the base for a planned October 1945 invasion of Java that was cancelled after the Japanese surrendered in August.