After commissioning, Simon Lake sailed from Bremerton on January 16, 1965 for Pearl Harbor on her shakedown cruise and return to Bremerton on February 17 for six-week yard availlability period. She steam out of Bremerton on April 16, 1965 and proceeded to Charleston, SC, via the Panama Canal.

USS Simon Lake arrived at Charleston on May 1, 1965 to tend the submarines there. In 1966, USS Simon Lake sailed for Holy Loch, Scotland, where she relieved USS Hunley (AS-31). The USS Simon Lake served in Holy Loch, Scotland for nearly, four years, departing for Bremerton in May 1970.

That July, the ship completed her first overhaul which lasted until March 1971. The USS Simon Lake returned to Charleston in April 1971 and aerved there until she relieved USS Holland (AS-32) in Rota, Spain in December 1972. In January 1977, the ship got underway for Charleston to undergo a complex overhaul.

Following her overhaul she relieved USS Hunley (AS-31) as the resident tender in Charleston. In July 1979, Simon Lake relocated to King's Bay, Georgia where she became the first tender at the newly established refit site there. Her outstanding repair work resulted in her receiving the 1982, 1984, and 1985 Battle Efficiency "E" awards.

In August 1985, she conducted a homeport change to Pascagoula, Mississipp to conduct an overhaul. After the overhaul, she return to Charleston in October 1986 where she completed routine upkeeps until May1987. In May 1987, she again relieved USS Hunley (AS-31) in Holy Loch, Scotland. She received the 1988 and 1991 Battle Efficiency "E" awards and was awared the Meritorious Unit Commendation in 1992.

While homeported in joly Loch, she steamed an average of 350 days a year. In March 1992 (after being the last tender in Holy Loch), Simon Lake returned to Norfolk to conduct an extensive overhaul. After completion of the overhaul in March 1993, she departed for her new homeport of La Maddalena, Italy where she turned over with USS Orion (AS-18). For superior service to the fleet, she received both the Battle Efficiency "E" and Meritorious Unit Commendation awards for 1994.

In March 1998, the transited the Suez Canal enroute to the United Arab Emirates where she supported Operation Southern Watch in the Arabian Gulf. Her outstanding performance during 47 availabilities led to her receiving the Navy Commendation and Armed Forces Expeditionary Medal.

In June 1998, she returned to La Maddalena, Italy. Simon Lake's performance during her last two years of service was particcularly noteworthy. Not only did she received the awards associated with the Arabian Gulf but she was nominated for the SECDEF maintenance award, received the 1997 and 1998 Battle Efficiency "Es", the 1998 CNO Safety Award, the Golden anchor award, and she became the first surface ship receive both the Enlisted Surface Warfare and the Surface warfare Officer pennants.

After being relieved by USS Emory S. Land (AS-39), Simon Lake departed La Maddalena on May 11,1999 and crossed the Atlantic for Norfolk, Virginia to be decommissioned.

During her 36 years of dedicates service, Simon Lake provided all aspect of logistical and repair support for and average of 45 submarine and surface ship availabilities, consisting over 5,000 vital repair jobs, annually. serving over 20 years as a forward-deployed tender, she served as an ambassador for the United States, showing the flag and entertaining foreign dignitaries during nearly 100 port visits in foeign countries.