The film is set during a fictitious Shuttle Explorer's STS-157 mission. Dr. Ryan Stone (Bullock) is a medical engineer on her first space shuttle mission aboard the Space Shuttle Explorer. She is accompanied by veteran astronaut Matt Kowalski (Clooney), who is commanding his final expedition. During a spacewalk to service the Hubble Space Telescope, Mission Control in Houston warns the team about a Russian missile strike on a defunct satellite, which has caused a chain reaction forming a cloud of space debris. Mission Control orders that the mission be aborted. Shortly after, communications with Mission Control are lost, though the astronauts continue to transmit, hoping that the ground crew can still hear them.
High-speed debris strikes the Explorer and Hubble, and detaches Stone from the shuttle, leaving her tumbling through space. Kowalski soon recovers Stone and they make their way back to the space shuttle. They discover that the shuttle has suffered catastrophic damage and the crew is dead. They use the thruster pack to make their way to the International Space Station (ISS), which is in orbit only about 900 mi (1,450 km) away. Kowalski estimates they have 90 minutes before the debris field completes an orbit and threatens them again.
En route to the ISS, the two discuss Stone's life back home and the death of her young daughter. As they approach the substantially damaged but still operational ISS, they see its crew has evacuated in one of its two Soyuz modules and that the parachute of the other capsule has accidentally been deployed, rendering it useless for returning to Earth. Kowalski suggests the remaining Soyuz be used to travel to the nearby Chinese space station Tiangong, 100 mi (160 km) away, and board one of its modules to return safely to Earth. Out of air and maneuvering power, the two try to grab onto the ISS as they fly by. Stone's leg gets entangled in Soyuz's parachute cords and she is able to grab a strap on Kowalski's suit. Despite Stone's protests, Kowalski detaches himself from the tether to save her from drifting away with him, and she is pulled back towards the ISS. As Kowalski floats away, he radios her additional instructions and encouragement.
Nearly out of oxygen, Stone manages to enter the ISS via an airlock but must hastily make her way to the Soyuz to escape a fire. As she maneuvers the capsule away from the ISS, the tangled parachute tethers prevent Soyuz from separating from the station. She spacewalks to release the cables, succeeding just as the debris field completes its orbit and destroys the station. Stone aligns the Soyuz with Tiangong but discovers the craft's engine has no fuel. After a brief radio communication with a Greenlandic Inuit fisherman and listening to him cooing a baby, Stone resigns herself to being stranded and shuts down the oxygen supply of the cabin in order to commit a painless suicide. As she begins to lose consciousness, Kowalski appears outside and enters the capsule. Scolding her for giving up, he tells her to rig the Soyuz's landing rockets to propel the capsule toward Tiangong. Possibly alluding to Kowalski's appearance being metaphysical in nature, she tells him to give her deceased daughter a message. Stone then sees that Kowalski is not actually there, but the interaction has nonetheless given her new strength and the will to live on. She restores the flow of oxygen and uses the landing rockets to navigate toward Tiangong.
Unable to dock the Soyuz with the station, Stone ejects herself via explosive decompression and uses a fire extinguisher as a makeshift thruster to travel to Tiangong. Space debris knocks Tiangong from its trajectory, and it begins rapidly deorbiting. Stone enters the Shenzhou capsule just as Tiangong starts to break up on the upper edge of the atmosphere. As the capsule re-enters the Earth's atmosphere, Stone hears Mission Control over the radio tracking the capsule. It lands in a lake, but dense smoke due to an electrical fire inside the capsule forces Stone to evacuate immediately. Opening the capsule hatch allows water to rapidly fill the capsule, which sinks, forcing Stone to shed her spacesuit underwater and swim ashore. She takes her first shaky steps on land, in the full gravity of Earth.
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