The F-106 served in the continental US, Alaska, and Iceland, as well as for brief periods in Germany and South Korea. The F-106 was the second highest sequentially numbered P/F- aircraft to enter service under the old number sequence (the F-111 was highest), before the system was reset under the 1962 United States Tri-Service aircraft designation system. In service, the F-106's official name, "Delta Dart," was rarely used, and the aircraft was universally known simply as the "Six."
Although contemplated for use in the Vietnam War the F-106 never saw combat, nor was it exported to foreign users. Following the resolution of initial teething problems – in particular an ejection seat that killed the first 12 pilots to eject from the aircraft – its exceptional performance made it very popular with its pilots. After the cancellation of their own Avro Arrow, the Canadian government briefly considered purchasing the F-106C/D.
In an effort to standardize aircraft types, the USAF was directed to conduct Operation Highspeed, a flyoff competition between the USAF F-106A and the U.S. Navy F4H-1 (F-4B) Phantom, which was not only as capable as the F-106 as a missile-armed interceptor, but could also carry as large a bomb load as the Republic F-105 Thunderchief fighter-bomber. The Phantom was the winner, but would first be tasked to escort and later replace the F-105 fighter-bomber in the late 1960s before replacing older interceptors in Air Defense Command in the 1970s.
Air-to-air combat testing suggested the "Six" was a reasonable match for the McDonnell Douglas F-4 Phantom II in a dogfight, with superior high-altitude turn performance and overall maneuverability (aided by the aircraft's lower wing loading). However, the Phantom had better radar – operated by an additional crewman – and could carry a load of up to four radar-guided Sparrow and four infrared Sidewinder missiles, while the Falcon missiles proved a disappointment for dogfighting over Vietnam. The F-4 had a higher thrust/weight ratio, superior climb performance, and better high speed/low-altitude maneuverability, and could be used as a fighter-bomber. Air combat experience over Vietnam showed the need for increased pilot visibility and the utility of a built-in gun, which had been added to the "E" variant of USAF Phantoms.
In 1972, some F-106As were upgraded in Project Six Shooter that involved fitting the F-106 with a new bubble canopy, a canopy without the metal bracing along the top. This greatly improved pilot visibility. Also added was an optical gunsight, and provision for a single M61 Vulcan 20 mm cannon. The M61 Vulcan had 650 rounds of ammunition in the center weapons bay and it replaced the AIM-26 Super Falcon or Genie.
The F-15A started replacing the F-106 in 1981, with the "Sixes" typically passed on to Air National Guard units. The F-106 remained in service in various USAF and ANG units until 1988.
Starting in 1986, many of the surviving aircraft were converted into drones, designated QF-106A, and used for target practice. The last was destroyed in January 1998. The drones were still capable of being flown as manned aircraft, such as for ferrying to a test; during the test they were flown unmanned. A handful of F-106s were retained by NASA for test purposes through 1998.