It is approximately 0.87 mi (1.4 km) northeast of Two Harbors, offshore from Isthmus Cove, and 1,540 ft (470 m) northwest of the closest coastal point.

The area where Two Harbors is located was originally referred to simply as the Isthmus of Catalina Island.

In 1864, during the Civil War, the Union Army sent 83 soldiers to the island to establish Camp Santa Catalina Island, both to protect the area from Confederate privateers and survey the isthmus and adjacent Catalina Harbor for the Bureau of Indian Affairs as a location for a future Indian reservation for "militant" tribes captured in the Bald Hills War.

The Ning Po, a Chinese merchant ship built in 1753 and involved in over a century of war, rebellion, and piracy, eventually found its way to Catalina and was converted into a tourist attraction in 1913.

The campus consists of a 30,000 square-foot (2,800 square-meter) laboratory building, a dormitory housing, a cafeteria, a hyperbaric chamber, and a large waterfront staging area complete with dock, pier, helipad, and diving lockers.

[7] A ferry run by the Catalina Island Company is available seasonally for transportation between Avalon and Two Harbors.