Conducting deterrence patrols during the Cold War, Kamehameha's armament was 16 Poseidon ballistic missiles plus 10–12 Mark 48 heavy torpedoes non-ADCAP (advanced capability).

Kamehameha joined the United States Pacific Fleet and the Blue Crew began her first deterrent patrol on 6 August 1966.

The information about Miss Charleston was in Commander Submarine Squadron 18's message of instructions for Kamehameha's arrival and had caused excitement among the bachelor junior officers.

Shortly after Kamehameha's arrival, she was ordered to sail on patrol earlier than scheduled to fill in for another boat that had suffered a casualty to the main engines.

[citation needed] Between 1974 and 1978 she belonged to Submarine Group 2, Squadron 16; homeported in New London, Connecticut, and advance-based in Rota, Spain.

[citation needed] During September–November 1976, Kamehameha spent time in Charleston, South Carolina, conducting SPECOPS with other units, then onto the AUTEC range for qualifications before resuming patrol duties after her return to Rota.

She finished sea trials in late 1982 and worked her way from Groton, Connecticut, to Port Canaveral, Florida, and then to Charleston for her complement of missiles.

In August 1991, with the deactivation of the Poseidon missile system, Kamehameha transferred from Holy Loch to Groton and performed non-deterrent patrol operations until July 1992 when she left for conversion.

In September 1992 through July 1993, at Mare Island Naval Shipyard in Vallejo, California, Kamehameha was converted to a Dry Deck Shelter/swimmer delivery platform, reclassified as an attack submarine, and given hull number SSN-642; her ballistic missile capability was removed, and she carried only torpedoes as armament.

[2] Upon her decommissioning, Kamehameha had been the longest serving nuclear-powered submarine in history, with a total service period exceeding 37 years.

[3] Kamehameha's scrapping via the Nuclear-Powered Ship and Submarine Recycling Program at Bremerton, Washington, began in October 2002 and was completed on 28 February 2003.

Her periscopes have been donated to Deterrent Park on Submarine Base Bangor, Washington, to become part of the USS Woodrow Wilson (SSBN-624) exhibit.