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

Primary payload was the Spacelab module. It was the first docking maneuver between an U.S. and a Russian spacecraft since 20 years. Following a two days solo flight the Atlantis docked to the MIR space station on June 29, 1995.

Other prime objectives were on-orbit joint United States of America-Russian life sciences investigations aboard SPACELAB/MIR, logistical resupply of the MIR and recovery of US astronaut Norman E. Thagard.

Secondary objectives included filming with the IMAX camera and the Shuttle Amateur Radio Experiment-II (SAREX-II) experiment.

STS-71 marked a number of historic firsts in human spaceflight history: the 100th U.S. human space launch conducted from the Cape; first U.S. Space Shuttle-Russian Space Station docking and joint on-orbit operations; largest spacecraft ever in orbit; and the first on-orbit changeout of a Shuttle crew.

For five days, about 100 hours in total, joint U.S.-Russian operations were conducted, including biomedical investigations, and transfer of equipment to and from MIR. Fifteen separate biomedical and scientific investigations were conducted, using the Spacelab module installed in the aft portion of Atlantis's payload bay, and covering seven different disciplines: cardiovascular and pulmonary functions; human metabolism; neuroscience; hygiene, sanitation and radiation; behavioral performance and biology; fundamental biology; and microgravity research. The MIR-18 crew served as test subjects for investigations. Three MIR-18 crew members also carried out an intensive programme of exercise and other measures to prepare for re-entry into gravity environment after more than three months in space.

Numerous medical samples as well as disks and cassettes were transferred to Atlantis from MIR, including more than 100 urine and saliva samples, about 30 blood samples, 20 surface samples, 12 air samples, several water samples and numerous breath samples taken from MIR-18 crew members. Also moved was a broken Salyut 5 computer. Transferred to MIR were more than 450 kilograms (990 lb) of water generated by the orbiter for waste system flushing and electrolysis; specially designed spacewalking tools for use by the MIR-19 crew during a spacewalk to repair a jammed solar array on the Spektr module; and transfer of oxygen and nitrogen from Shuttle's environmental control system to raise air pressure on the station, to improve MIR's consumables margin

The MIR resident crew was exchanged. Anatoli Soloviyov and Nikolai Budarin became the 19th resident crew. The former 18th resident crew (Vladimir Dezhurov, Gennadi Strekalov, Norman Thagard) returned to Earth with STS-71.

Later Anatoli Soloviyov and Nikolai Budarin performed three EVAs on July 14, 1995 (5h 34m), July 19, 1995 (3h 08m) and July 21, 1995 (5h 50m). The separation of STS-71 was observed from the also separated Soyuz spacecraft.

Anatoli Soloviyov and Nikolai Budarin landed on September 11, 1995 at 06:52 UTC with Soyuz TM-21 spacecraft.