One of the most difficult tasks was establishing and executing the vast training program required for the Blue and Gold crews of each submarine.

In the early dawn of 27 May 1964, Daniel Boone surfaced off Diamond Head, Hawaii, after completing a submerged transit from the mainland, and steamed into Pearl Harbor, where she became the first Polaris submarine ever to enter the port.

On the morning of 29 November 1964, Proteus entered Apra Harbor, where she commenced setting up the third FBM replenishment site to support Polaris submarines.

On the morning of 14 October 1971, the submarine tender USS Hunley entered Apra Harbor, Guam and immediately upon mooring at Polaris Point, set about the complex chore of relieving Proteus.

The departure of James Monroe, Daniel Webster, Henry Clay, and the arrival of Theodore Roosevelt resulted in the following units assigned to the squadron: Proteus (flagship), George Washington, Patrick Henry, Theodore Roosevelt, Robert E. Lee, Abraham Lincoln, Ethan Allen, Sam Houston, Thomas A. Edison, John Marshall and Thomas Jefferson.

On 30 September 1981, Submarine Squadron Fifteen ended its eighteen-year existence when it was disestablished in ceremonies on board Proteus in Apra Harbor, Guam.

Submarine Squadron Fifteen was also actively involved in the force protection decisions and efforts of the Naval Station on board COMNAVMARIANAS immediately following the 11 September 2001 attacks.

Submarine Squadron Fifteen personnel, assisted by sailors from Frank Cable, participated in post-typhoon recovery actions.

A major fire at the island's gasoline storage facility delayed the recovery effort by limiting the availability of fuel for vehicles and emergency generators.

Structures throughout the island, including homes, hospitals, businesses, governmental and military facilities, airports, and harbors were damaged or destroyed.

Loss of life was minimized and basic services were rapidly restored due to the timely, aggressive and selfless effort of military personnel assigned to units of Submarine Squadron Fifteen.

On 23 December 2003 City of Corpus Christi completed the first-ever mission deployment in support of Commander Seventh Fleet operations by a forward based attack submarine home-ported in Guam.

On 8 January 2005 at 02:43 GMT, San Francisco struck an undersea mountain about 364 nautical miles (675 km) southeast of Guam while operating at flank (maximum) speed and more than 500 feet (152 m) deep.

The collision was so serious that the vessel was almost lost; accounts detail a desperate struggle for positive buoyancy to surface after the forward ballast tanks were ruptured.