During the Vietnam War Joseph Strauss served as plane guard for aircraft carriers on Yankee Station in the Tonkin Gulf, participated in Sea Dragon operations, patrolled on search and rescue duties and carried out naval gunfire support missions.

Joseph Strauss departed Philadelphia on 6 June 1963 for a brief cruise to Puerto Rico and Willemstad, Curaçao, and then transited the Panama Canal to join the Pacific Fleet on the western seaboard.

She arrived at Long Beach Naval Shipyard on 13 July 1963 for alterations, followed by tactics out of San Diego north to Seattle, Washington.

Following upkeep in Subic Bay from 1–10 March, Joseph Strauss sailed with ships of the Royal Thai Navy for exercises in the Gulf of Thailand.

From 24 April 1965, Joseph Strauss, together with Ernest G. Small, was part of the first advanced search and rescue/anti-air warfare (SAR/AAW) picket team in the Gulf of Tonkin to support U.S. air strike operations against North Vietnam.

Her ensuing 27 days as flagship of the SAR/AAW picket unit were highly successful, establishing operational procedures and capabilities which remain destroyer standards.

On 28 October 1965, she fired her first shots in anger, expending 217 5-inch shells in support of a combined ARVN-Marine Corps search-and-destroy operation against the Viet Cong.

Joseph Strauss returned to the Gulf of Tonkin 10 February 1966 and remained active in the war zone until heading for Hong Kong exactly one month later.

Twenty minutes after the first sighting, as Samuel B. Roberts was backing clear of the minefield, she struck a submerged mine nearly ripping the warship in half.

The battle, the largest for American surface forces since World War II, sank two Iranian warships and it also marked the first surface-to-surface missile engagement in U.S. Navy history.

The three ships of SAG Charlie (Wainwright, Simpson, and Bagley) closed on Joshan, destroying the Iranian vessel with naval gunfire.

Fighting continued when the Iranian frigate Sahand departed Bandar Abbas and challenged elements of an American surface group.

Joseph Strauss was decommissioned on 1 February 1990, transferred to Greece on 1 October 1992 and renamed Formion (D220), for the Athenian Admiral Phormio, and stricken from the Naval Vessel Register on 11 January 1995.