In 2067, ex-NASA pilot Cooper is forced to work as a farmer. He ignores his daughter, Murph, when she claims a ghost is communicating to her through her bookshelf, but later finds dust particles forming an inexplicable pattern on Murph's bedroom floor. He investigates, arriving at a secret NASA facility where Professor Brand explains that blight, dust storms and failing crops have rendered humanity incapable of surviving on Earth. NASA's current, secret mission involves engineering a way for humans to escape the Earth while finding another habitable planet. Brand claims to be working on a gravity equation to make this possible, and asks Cooper to pilot the mission. Cooper agrees, promising a distraught Murph that he will return. He pilots a shuttle carrying scientists Romilly, Doyle, and Brand’s daughter Amelia to dock with the spacecraft Endurance. The ship is headed towards a wormhole that mysteriously appeared near Saturn decades ago.

The Endurance passes through the wormhole into another galaxy with a planetary system orbiting a supermassive black hole called Gargantua. The crew intends to investigate three planets, each previously explored by NASA volunteers, who shared positive reports for habitability. The first planet is an aqua planet with massive tidal waves and no dry land. Doyle drowns, and Amelia and Cooper fly back to the Endurance, only to find that decades have passed due to the time slippage caused by the planet's proximity to Gargantua. Romilly, having remained onboard, has aged twenty-three years. Cooper replays messages from Earth, learning that Murph is now his age and has become a scientist working with Brand.

The crew journey to the second planet, where its previous investigator, Mann, falsified data to ensure a NASA mission to his planet so he could be rescued. Romilly is killed by Mann's booby-trap, and Mann attempts to hijack the Endurance but fails to dock properly, blowing out the hatch and killing himself in the process. Cooper and Amelia catch up with the damaged Endurance and dock safely. With limited resources available to use their engines, Cooper proposes a slingshot move around Gargantua, using its gravity to propel them toward the final planet. To shed weight, Cooper sacrifices himself at the last minute, dropping into the black hole and leaving Amelia to complete the journey.

Falling past the event horizon, Cooper finds himself inside a five-dimensional tesseract. He deduces that it was placed there by future humans with access to higher dimensions, as was the wormhole. He realizes that by using gravity, he is able to send messages to Murph and his past self. On Earth, Murph visits her childhood house after Professor Brand's death. She finds her father's old watch on her bookshelf, and notices the seconds-hand moving irregularly. She initially believes her "ghost" is back, only to realize that it was Cooper all along, sending her messages from a higher dimension. Cooper feeds Murph scientific data about the black hole's singularity, which she eventually uses to solve the gravity-equation, helping humanity escape the Earth.

His mission is now complete, and Cooper is ejected by future beings from the tesseract. He is sent back through the wormhole and picked up by a ranger orbiting Saturn. Due to the time slippage around Gargantua, almost ninety years have passed in Earth-time since Cooper left, though he has barely aged. He awakens on a space station and reunites with Murph, now a celebrated scientist who helped humans survive extinction. Nearing death, she advises Cooper not to wait around to see her die, and urges him to find Brand, who may have settled on the other planet that could become their new home. Cooper steals a spacecraft and sets off on his new journey. On the other planet, Amelia is building a new colony for future humans to inhabit. She removes her helmet and breathes the air, showing that the planet is capable of supporting life.