Launch from Cape Canaveral (KSC); landing on Edwards AFB.

The launch was first scheduled for May 16, 1990. Following Flight Readiness Review (FRR), announcement of firm launch date delayed to change out a faulty freon coolant loop proportional valve in orbiter's coolant system. At subsequent Delta FRR, date set for May 30. Launch on May 30, 1990 scrubbed during tanking due to minor hydrogen leak in tail service mast on mobile launcher platform and major leak in external tank/orbiter 17 inch (432 mm) quick disconnect assembly. Hydrogen also detected in orbiter's aft compartment believed associated with leak involving 17 inch (432 mm) umbilical assembly. Launch rescheduled for September 06, 1990. During tanking, high concentrations of hydrogen detected in orbiter's aft compartment, forcing another postponement. NASA managers concluded that Columbia had experienced separate hydrogen leaks from beginning: one of umbilical assembly (now replaced) and one or more in aft compartment which had resurfaced. Suspicion focused on package of three hydrogen recirculation pumps in aft compartment. Columbia transferred to Pad 39-B October 08, 1990 to make room for Atlantis on Mission STS-38. Tropical storm Klaus forced rollback to VAB October 09, 1990. Vehicle transferred to Pad 39-B again October 14, 1990. Mini-tanking test conducted October 30, 1990, using special sensors and video cameras and employing a see-through Plexiglas aft compartment door. Liftoff December 2, 1990 was delayed 21 minutes to allow the Air Force range time to observe low-level clouds that might impede tracking of Shuttle ascent.

Vance Brand became the oldest astronaut to fly into space.

Primary objectives were round-the-clock observations of celestial sphere in ultraviolet and X-ray astronomy with ASTRO-1 observatory consisting of four telescopes: Hopkins Ultraviolet Telescope (HUT); Wisconsin Ultraviolet Photo-Polarimeter Experiment (WUPPE); Ultraviolet Imaging Telescope (UIT); and Broad Band X-Ray Telescope (BBXRT). Ultraviolet telescopes mounted on Spacelab elements in cargo bay were to be operated in shifts by flight crew.

The loss of both data display units (used for pointing telescopes and operating experiments) during mission impacted crew-aiming procedures and forced ground teams at Marshall Space Flight Center to aim ultraviolet telescopes with fine-tuning by flight crew. BBXRT, also mounted in cargo bay, was directed from outset by ground-based operators at Goddard Space Flight Center and not affected. But all in all only 70% of planned science data were achieved.

Other experiments were: Shuttle Amateur Radio Experiment-2 (SAREX-2); ground-based experiment to calibrate electro-optical sensors at Air Force Maui Optical Site (AMOS) in Hawaii; and crew conducted Space Classroom Program: Assignment: The Stars, to spark student interest in science, math and technology. Crew experienced trouble dumping waste water due to clogged drain, but managed using spare containers.

The mission was cut short one day due to impending bad weather at primary landing site.