This mission was officially designated Skylab 2 (Skylab 1 was the launch of the station itself), but it was almost universally referred to as Skylab I (with a Roman Numeral). The human missions were launched atop the Saturn 1B launch vehicles.

The unscreen/meteorite shield had torn off during launch, taking with it one of the two solar panels and badly damaging the other, which would not deploy. The crew's first priority was to fashion some kind of sunshield, because the high temperatures threatened to spoil the food supply and made the interior of the station too hot to occupy, as well as releasing toxic gases from the plastics on-board and ruin all the photographic film. While staying in the more pleasant Apollo Command Module, they used a "parasol" made by JSC's Tech Services Division from a spacesuit material covered in kapton tape to shield the Skylab from the sunlight, and the temperature dropped enough that they were able to enter.

This mission once again more than doubled the previous endurance record in space, just set by the astronauts of Skylab I just a month earlier. After an early bout with motion sickness, the crew settled down for their two-month mission, deploying a second sun shield on a space walk lasting six hours, 30 minutes. They conducted many experiments, and brought with them live spiders to conduct a student-designed experiment to see what kinds of webs the spiders would spin in weightlessness. Also on this mission the astronauts finally got to test the Astronaut Maneuvering Unit, or AMU, which had initially been carried into space aboard Gemini IX but could not be tested then because of problems with the old Gemini space suit.

At 84 days, 1 hour, 15 minutes and 31 seconds, Skylab III (actually oficially designated "Skylab 4") remains by far the longest American space flight, a record that will certainly stand until the permanent human occupation of space begins with the international Space Station. To help keep the crew in physical condition during their almost three months in orbit, they walked treadmills and rode an on-board stationary bicycle, and came home in far better condition than had the previous Skylab crews. Among the thousands of experiments they conducted during this long, long flight, the astronauts took four space walks, including one on Christmas Day to observe the comet Kohoutek.