The launch was delayed by one hour and thirty-eight minutes due to unseasonable and unusual light winds, and the need to replace fuses in the cooling systems of two crew members' flight suits.

It was quickly determined that the cabin pressure had been increased slightly by the activation of the oxygen systems in the crew's flight suits, and the launch was conducted without further delay.

The orbiter sustained only minor Space Shuttle thermal protection system tile damage, and the post-Challenger redesigned solid rocket booster segment joints showed no signs of leakage or overheating.

After ascent, the Flash Evaporator System for cooling the orbiter iced up and shut down, increasing the crew cabin temperature to approximately 31 °C (88 °F).

During STS-26, Discovery became the first spacecraft to fly in space equipped with a VCU (Voice Control Unit), a computer capable of recognising and responding to human speech.

It was concluded that weightless conditions caused a fundamental change in human speech, making the templates created prior to liftoff virtually useless on orbit.

Discovery landed on Runway 17, Edwards Air Force Base, California, at 12:37:11 p.m. EDT on October 3, 1988, after a mission duration of approximately 4 days, 1 hour, 0 minute, and 11 seconds.

TDRS-C, which became TDRS-3 in orbit, and its attached Inertial Upper Stage (IUS), were deployed from Discovery's cargo bay six hours and 13 minutes into the flight.

The materials processing experiments included two Shuttle Student Involvement Projects, one on titanium grain formation and the other on controlling crystal growth with a membrane.

Another materials science experiment, the Physical Vapor Transport of Organic Solids-2 (PVTOS-2), was a joint project of NASA's Office of Commercial Programs and the 3M company.

Three life sciences experiments were conducted, including one on the aggregation of red blood cells, intended to help determine if microgravity can play a beneficial role in clinical research and medical diagnostic tests.

[4] Kathryn D. Sullivan chose the wakeup music for STS-26, including a contribution from Robin Williams, who provided a pastiche of his Good Morning, Vietnam radio greeting.