After purchase of Alaska in 1867, American trappers and traders intensified the outrages, prompting the setting aside of lands for this Refuge and an international treaty protecting sea otters and fur seals. Teddy Roosevelt established some of the first units of the refuge in 1909.

During World War II, Japanese swept into the Aleutians, bombing Dutch Harbor and seizing the refuge islands of Kiska and Attu. Allied forces fought the long and bloody Aleutian Campaign to recapture these islands. Bases, observation posts and airfields were hastily constructed on dozens of refuge islands.

The legacy of the war remains inspite of ongoing cleanup efforts. Debris, toxic chemicals and historic remnants are scattered throughout the chain. The military remained after the war building a large base, now decommissioned, on Adak in response to the Cold War threat posed by the nearby Soviet Union. In the 1960's and 70's three underground nuclear bombs were tested on the refuge island of Amchitka. Cannikan, in 1971, was the largest underground nuclear blast in U.S. history. The ecological consequences of these blasts are still being investigated.

In 1980, President Carter created the refuge as we know it today by combining 11 existing refuges plus some additional land into the Alaska Maritime National Wildlife Refuge.