The mission, crewed by Jack R. Lousma and C. Gordon Fullerton, involved extensive orbital endurance testing of Columbia itself, as well as numerous scientific experiments.

STS-3 was the first shuttle launch with an unpainted external tank, and the only mission to land at the White Sands Space Harbor near Alamogordo, New Mexico.

The crew found that prolonged exposure to the Sun caused the cargo bay doors to warp slightly, preventing them from closing fully.

[7] In addition, in its payload bay, Columbia again carried the Development Flight Instrumentation (DFI) package, and OSS-l (named for the NASA Office of Space Science and Applications) which consisted of a number of instruments mounted on a Spacelab pallet, intended to obtain data on the near-Earth environment and the extent of contamination caused by the orbiter itself.

The orbiter's toilet malfunctioned on first use resulting in, according to Lousma, "eight days of colorful flushing"; one Auxiliary Power Unit (APU) overheated[7] (but worked properly during descent); both crew members experienced some space sickness; and on March 26, 1982, three communications links were lost.

A large-scale equipment movement (reportedly "40 train carloads") from Edwards Air Force Base to White Sands was undertaken before and during the mission, to ensure that a landing could be fully supported.

[7] As on the previous day's wave off, strong westerly high level winds were in excess of system verification values.

As a result, Columbia had to fly a less desirable high "right base" turn onto final approach instead of the more usual and forgiving overhead pattern.

The final approach was in part flown by the shuttle's autopilot, but the autoland software was not complete so it could not include an automatic landing.

Rolling out on final approach, the autopilot was reengaged, and responded by closing the speedbrakes (despite the orbiter being on profile), resulting in increased speed.

Lousma left the autopilot activated in order to gather data on its behavior, but disconnected it again at a very late stage to touch down manually.

[11] Former Administrator of NASA Charles F. Bolden Jr. stated that Lousma was trained to disengage autoland by moving the control stick.

While on a post-mission goodwill tour in Beijing, Lousma displayed a photo he had taken from space of a "beautiful emerald-colored lake" in China and was surprised by the audience reaction.