Wild Weasel operations:
561st Tactical Fighter Squadron F-105G over Southeast Asia in the summer of 1972
Wild Weasel operations became the squadron's primary mission in mid-1970, when the squadron exchanged its single seat F-105s for two seat F-105G Thunderchiefs. In April 1972, the squadron established Detachment 1 at Korat Royal Thai Air Force Base, Thailand and flew combat Wild Weasel missions. The detachment was discontinued in September, but crews and planes of the squadron continued to fly missions until late January 1973. The squadron was awarded the Air Force Outstanding Unit Award with "V" Device and the Vietnamese Gallantry Cross with Palm for this period. A plane from the 561st was the last F-105 shot down in the Vietnam War. It was hit by a surface-to-air-missile on 16 November 1972; the crew was rescued. One of the surviving aircraft from the squadron is on display at the National Museum of the United States Air Force with the 561st Squadron's markings.

On 1 July 1973, the 561st moved to George Air Force Base and joined the 35th Tactical Fighter Wing. At George, the squadron mission was primarily the training of Wild Weasel crews. The squadron continued to fly the F-105G until 1980, when it began transitioning into the McDonnell F-4G Phantom II advanced Wild Weasel, completing the transition the following year. In August 1990, the Wild Weasels deployed to Sheikh Isa Air Base, Bahrain and during Operation Desert Storm flew over 2,400 sorties logging more than 8,000 combat hours. After the war, the squadron was inactivated on 30 June 1992.

The squadron was activated at Nellis Air Force Base as part of the 57th Operations Group on 1 February 1993. the 561st soon deployed to Incirlik Air Base in support of Operation Provide Comfort and returned to Southwest Asia at Dhahran Air Base in Saudi Arabia, supporting Operation Southern Watch and Operation Vigilant Warrior. The 561st was also employed as an "Aggressor" squadron during RED FLAG exercises. In 1994, the 561st became the largest fighter squadron in the United States Air Force.[citation needed] It maintained a continuous deployment to the Middle East until inactivating in October 1996.