The July 2006 earthquake sequence occurred in the area separating the rupture zones of the 1965 M8.7 Rat Islands earthquake to the west and the 1957 M8.6 Andreanof Islands earthquake to the east. The westernmost area of the 1957 fault zone was reruptured repeatedly in the 1986 M8.0 and 1996 M7.9 earthquakes. The eastern portion of the 1965 fault zone was reruptured recently in the M7.7 earthquake on November 17, 2003.

All of these events ruptured the boundary between the subducting Pacific and overriding North American plates. The Aleutian megathrust, where the two plates are being forced directly into one another, is one of the world's most active seismic zones. More than one hundred earthquakes of magnitude seven or larger have occurred along this boundary in the past hundred years, or one magnitude 7+ earthquake every year or two.