The RF-101C was a single-seat photographic reconnaissance version of the Voodoo interceptor that had first entered service with the USAF in 1958.  The RF-101C was one of the first US jet aircraft to be based in Southeast Asia.  On 18 October 1961 four aircraft from the 15th TRS based at Kadena AB, Japan deployed to Tan Son Nhut under the code name Pipe Stem to photograph suspected Viet Cong strongholds.  Three weeks later, on 6 November, they were replaced by another detachment of four RF-101Cs from the 45th TRS (code-name Able Mable) that deployed from Misawa AB, Japan to Don Muang airport in Thailand.  The two detachments made reconnaissance flights over South Vietnam and Laos until the Geneva talks brought a temporary cessation of flights over Laos in July 1962.  The Able Mable detachment moved to Tan Son Nhut in December 1962 as the concentration of effort shifted from Laos to South Vietnam.  In the early years of the war four Voodoo squadrons (the 15th from Kadena AB, the 45th from Misawa AB, and the 20th and 29th from Shaw AFB, South Carolina) provided air and ground crews for the detachments based in South Vietnam and Thailand.  Two more aircraft were added to the Able Mable detachment on 1 April 1963 and by August 1964 a total of 16 RF-101Cs were based at Tan Son Nhut.  The 20th TRS was the only RF-101C unit assigned to Southeast Asia in full strength and was based at Tan Son Nhut before moving to Udorn in September 1966.

In the spring of 1964 the situation in Laos became more serious and the US decided to resume reconnaissance flights over the country.  This time the flights were of a more tactical nature, supplying targeting information on Pathet Lao troop movements to Royalist forces.  Under the code name Yankee Team the joint US Air Force and Navy operation commenced on 19 May when four Able Mable aircraft flew sorties over Laos.  In March 1965 the RF-101s started reconnaissance flights (code-named Blue Tree) over North Vietnam, a development facilitated by moving four aircraft of the 15th TRS from Tan Son Nhut to Udorn to start a detachment code named Green Python.

The role of the RF-101C evolved into four types of reconnaissance mission: surveillance, concentrating on lines of communications; pre-strike reconnaissance for targeting purposes; post-strike reconnaissance for battle damage assessment; and (from mid-1965) searching for SAM sites.  The very early missions were escorted by F-100s, later replaced by F-105s and F-4s.  However, the reconnaissance aircraft often flew unescorted singly or in pairs, often preferring this to flying with escorts.  Unencumbered by large amounts of ordnance, the Voodoo was actually faster than its escorts and recce pilots relied primarily on speed, tactics and terrain masking for survival.  In April 1966 a study showed that many of the Voodoos shot down by AAA were the wingmen who were following their leaders and were hit by AAA aimed at the lead aircraft which usually escaped unscathed.  The result was that from this date most reconnaissance missions were flown by single aircraft.  However, this caused problems in determining the cause of attrition when aircraft did not return nor did it give the redundancy of a second aircraft to complete the mission if the first aircraft was shot down or had to abort.

Probably because the Voodoos spent much of their time at low level, the aircraft was one of the first USAF types to receive the three tone tactical camouflage in mid-1965.  Curiously, the Voodoo squadrons were among the last to adopt squadron tail codes when they came into use later in the war.