The contract to build SSN 751 was awarded on November 30, 1982 and her keel was laid on August 9, 1985. She was launched on December 6, 1986 and commissioned on August 6, 1988, with Cmdr. Charles Young in command.

USS San Juan was the first Los Angeles class (688-class) submarine to receive a number of significant improvements to the class's basic design, creating the 688I (for "improved 688"). SSN 751 and all following submarines in her class are quieter, incorporate an advanced AN/BSY-1 "busy one" combat control system/sonar suite, and have dedicated tubes for vertical launch of the Tomahawk cruise missile. The externally visible changes are also significant, as the San Juan had her forward diving planes moved from the sail to the bow and made retractable. Together, the retractable bow planes, strengthening of the sail, and installation of additional depth control and support systems make it possible for San Juan to break through polar and near-polar ice as a part of 'normal' ship operations.

On March 19, 1998, USS San Juan collided with USS Kentucky (SSBN 737) south of Long Island, New York. The balistic-missile submarine suffered damage to its rudder but no injuries occurred on either ship; the San Juan's forward ballast tank was breached, but the ship was able to surface and return to port.

February 21, 2003 The San Juan pulled to Souda Bay, Crete, for a scheduled port visit.

March 21, Thirty U.S. Navy and coalition warships, includinh USS San Juan, currently assigned to Naval Forces Central Command launched Tomahawk Land Attack Missiles (TLAMs) during military operations to disarm Iraq.

April 23, SSN 751 returned to Naval Submarine Base New London after having its regularly-scheduled six-month deployment extended. She was on patrol in the Mediterranean Sea when it was ordered to the Red Sea - tasked to remain on station and support Tomahawk missile strike operations into Iraq as part of Operation Iraqi Freedom.

April 27, 2004 Cmdr. Harvey L. Guffey relieved Cmdr. Edward L. Takesuye as commanding officer of USS San Juan in a ceremony at Shepherd of the Sea Chapel.

October 18, 2005 The Los Angeles-improved class fast-attack submarine arrived in Souda Bay, Crete, for a brief port call. The ship is currently on a scheduled deployment in support of the Global War on Terrorism.

July 3, 2006 USS San Juan fired the Mark 48 torpedo that deliberately sank the USNS Butte in a target exercise. She is also a primary testing platform for new, advanced systems being developed by the U.S. Navy.

March 13, 2007 SSN 751 was the subject of a search & rescue mission by elements of the Enterprise Carrier Strike Group when a red flare was spotted in her projected vicinity, suggesting an emergency. Communications were established by the early hours of the next day (the San Juan had been submerged) and no problems were indicated.

May 22, USS San Juan pulled to Souda Bay, Crete, for a routine port visit. She departed her homeport of Groton, Conn., earlier this month for deployment in support of maritime operations.

March 26, 2008 The San Juan is currently in the Groton waterfront's dry dock undergoing a scheduled rehabilitation period.

November 4, 2009 USS San Juan, commanded by Cmdr. Oliver Lewis, arrived in Simon's Town to participate in a series of first-ever, at-sea engagements with the South African Navy.

December 1, SSN 751 returned to NSB New London after a six-month deployment to the U.S. European (EUCOM) and African Command (AFRCIOM) areas of responsibility (AoRs). The submarine also visited Souda Bay, Greece; Diego Garcia; and Port Victoria, Seychelles.

April 8, 2010 USS San Juan arrived at Portsmouth Naval Shipyard (PNSY) in Kittery, Maine, for maintenance work and several system upgrades.