Hancock reached Japan on 19 November and soon was on patrol at Yankee Station in the Gulf of Tonkin. She remained active in Vietnamese waters until heading for home early in the spring of 1965.
November found the carrier steaming back to the war zone. She was on patrol off Vietnam on 16 December; and, but for brief respites at Hong Kong, the Philippines, or Japan, Hancock remained on station launching her planes for strikes at enemy positions ashore until returning to Alameda on 1 August 1966. Her outstanding record during this combat tour won her the Navy Unit Commendation.
Following operations off the West Coast, Hancock returned to Vietnam early in 1967 and resumed her strikes against Communist positions. After fighting during most of the first half of 1967, she returned to Alameda on 22 July and promptly began preparations for returning to battle.
In the summer of 1969 she was back in Alameda preparing for yet another deployment to southeast Asia. In July, while in pre-deployment night landing exercises, an F-8 came in too low and crashed into the round-down splitting the aircraft into two pieces which hurtled down the deck and erupted in a massive fuel fed fire. While no lives were lost, damage to the flight deck was extensive, resulting in a frenetic 24 x 7 repair effort to be ready by the deployment date.
Aircraft from Hancock, along with those from Ranger and Oriskany, joined with other planes for air strikes against North Vietnamese missile and antiaircraft sites south of the 19th parallel in response to attacks on unarmed U.S. reconnaissance aircraft on 21–22 November 1970 (Operation Freedom Bait). Hancock alternated with Ranger and Kitty Hawk on Yankee Station until 10 May 1971, when she was relieved by Midway.
Hancock, along with Coral Sea, was back on Yankee Station by 30 March 1972 when North Vietnam invaded South Vietnam. In response to the invasion, Naval aircraft from Hancock and other carriers flew tactical sorties during Operation Freedom Train against military and logistics targets in the southern part of North Vietnam. By the end of April, the strikes covered more areas in North Vietnam throughout the area below 20°25′ N. From 25–30 April, aircraft from Hancock's VA-55, VA-164, and VA-212 struck enemy-held territory around Kontum and Pleiku.