Some of the significant projects supported by B-52 008 included the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38.

The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space shuttle solid rocket booster casings. It also supported eight orbiter (space shuttle) drag chute tests in 1990. In addition, the B-52 served as the air launch platform for the first six Pegasus space boosters.

During its many years of service, the B-52 underwent several modifications. The first major modification was made by North American Aviation (now part of Boeing) in support of the X-15 program. This involved creating a launch-panel-operator station for monitoring the status of the test vehicle being carried, cutting a large notch in the right inboard wing flap to accommodate the vertical tail of the X-15 aircraft, and installing a wing pylon that enables the B-52 to carry research vehicles and test articles to be air-launched/dropped. Located on the right wing, between the inboard engine pylon and the fuselage, this wing pylon was subjected to extensive testing prior to its use. For each test vehicle the B-52 carried, minor changes were made to the launch-panel operator's station.

Built originally by the Boeing Company, the NASA B-52 was powered by eight Pratt & Whitney J57-19 turbojet engines, each of which produced 12,000 pounds of thrust. The aircraft's normal launch speed was Mach 0.8 (about 530 miles per hour) and its normal drop altitude was 40,000 to 45,000 feet. It was 156 feet long and had a wing span of 185 feet. The heaviest load it carried was the No. 2 X-15 aircraft at 53,100 pounds. Project manager for the aircraft was Roy Bryant.

Another B-52 (an A-model), Tail Number 003, also flew as a mothership, launching the X-15 and lifting bodies.