On her first patrol, Sam Houston, manned by the Blue Crew, operated continuously submerged for 48 days and two hours, then moored alongside the submarine tender USS Proteus (AS-19) in Holy Loch, Scotland.

On this patrol, she was the first fleet ballistic missile submarine to enter the Mediterranean Sea, where she joined North Atlantic Treaty Organization (NATO) forces.

On 10 August 1966, she returned to the United States for the first time since her deployment to Holy Loch in 1962 and commenced a major overhaul at the Portsmouth Naval Shipyard at Kittery, Maine.

On 27 November, she entered Charleston Naval Shipyard and began an extended in-port period, which included regular overhaul and the updating of her weapons and propulsion systems.

Gold crew under the command of J.P Wiekert transited the Panama Canal in August 1975 with stops in San Diego, Weapons Station Bremerton arriving at Pearl Harbor in early October 1975.

Sam Houston was reclassified as an attack submarine with hull number SSN-609 on 10 November 1980 and retained primarily for training, antisubmarine warfare exercises, and other secondary duties.

[3] Deactivated on 1 March 1991 while still in commission, Sam Houston began the Nuclear Powered Ship and Submarine Recycling Program at Puget Sound Naval Shipyard the same day.

She was formally decommissioned and stricken from the Naval Vessel Register on 6 September 1991 and finished the recycling program on 3 February 1992, when she was officially listed as scrapped.