Challenger launched from Kennedy Space Center on April 29, 1985 at 12:02 PM EDT and landed at Edwards Air Force Base on May 6 at 9:11 AM PDT. The shuttle orbited 111 times at an altitude of 222 nautical miles and at an inclination of 57 degrees and travelled 2.9 million miles. The mission lasted 7 days, 0 hours, 8 minutes, and 46 seconds.

The flight was first manifested as 51-E but it was rolled back from pad due to a timing problem with the TDRS-B payload. Mission 51-E was cancelled and the orbiter was remanifested with 51-B payloads. The launch on April 29 was delayed two minutes, 18 seconds due to a launch processing system failure.

The orbiter made its first crosswind landing at Edwards Air Force Base in California and returned to Kennedy Space Center on May 11, 1985.

The primary payload was Spacelab-3. This was the first operational flight for the Spacelab orbital laboratory series developed by the European Space Agency. Spacelab includes five basic discipline areas: materials sciences, life sciences, fluid mechanics, atmospheric physics, and astronomy.

The main mission objective with Spacelab-3 was to provide a high quality microgravity environment for delicate materials processing and fluid experiments. Two monkeys and 24 rodents were observed for the effects of weightlessness. Of the 15 Spacelab primary experiments conducted, 14 were considered successful. Two Get Away Specials were on board.

Challenger was crewed by Commander Robert F. Overmyer, Pilot Frederick  D. Gregory, Mission Specialists Don L. Lind, Norman E. Thagard, and William E Thornton, and Payload Specialists Lodewijk van den Berg and Taylor G. Wang.