"John S. McCain" departed on 7 March 1961 for another deployment with Seventh Fleet, spending six months off Laos and Vietnam. She resumed operations in Hawaiian waters after her return to Pearl Harbor on 25 September With the resumption of atmospheric nuclear testing by the Soviet Union some months later, the United States went ahead with plans for her own series of Pacific tests, and "John S. McCain" steamed to Johnston Island on 27 April 1962 to take part in the experiments. For the next six months she operated between Hawaii and Johnston Island, departing for her next cruise to the Far East on 28 November 1962. There she returned to patrol duties in the South China Sea and Gulf of Tonkin, aiding the South Vietnamese government in its fight against the Viet Cong. She also took part in Formosa Patrol in the Straits before returning to Pearl Harbor on 16 June 1963. Antisubmarine warfare exercises followed, and the ship got underway again on 23 March 1964 for operations with a hunter-killer group in Japanese and Philippine waters. During this cruise she took part in exercises with ships from other SEATO nations as well as units of the 7th Fleet. "John S. McCain" returned to Pearl Harbor on 11 August. She operated in Hawaiian waters until the spring of 1965. The destroyer returned to Pearl Harbor, and then sailed on a six-month deployment in the western Pacific. In the fall, "John S. McCain" steamed off South Vietnam. On 24 November 1965 she shelled Viet Cong positions. Two days later she sailed to Hong Kong and ended the year in Japan. After further operations in the Far East early in 1966, "John S. McCain" returned to the East Coast of the United States.