On Earth, crop blight has caused civilization to regress into a failing agrarian society. A widowed former pilot, Cooper, runs a farm with his father-in-law, son and young daughter, Murphy, who believes her room is haunted by a poltergeist trying to communicate by throwing books off her shelf. Cooper concludes Murphy's "ghost" is an unknown intelligence using gravitational waves to send a set of binary coordinates in the dust. These direct them to a secret NASA installation.
There, they meet one of Cooper's college professors, Dr. John Brand, who reveals that a wormhole, apparently created by an unknown alien intelligence, has opened near Saturn and leads to new planets in a distant galaxy. NASA had already sent through twelve astronauts led by Dr. Hugh Mann to identify habitable worlds. Three of the missions are sending back encouraging results; Miller, Edmunds and Mann, orbiting a supermassive black hole named Gargantua. Brand recruits Cooper to pilot the spacecraft Endurance to recover the scientists' data on the planets, while he continues to work on harnessing gravity for propulsion, to send humanity on space stations to one of the habitable worlds. As "Plan B", Endurance carries 5,000 frozen embryos to repopulate the race on a new world. Cooper's decision to accept devastates Murphy, and they part on bad terms.
Cooper's Endurance crew consists of Brand's daughter, Amelia, scientists Romilly and Doyle, and robots TARS and CASE. Traversing the wormhole, they head to Miller's planet, stopping there only briefly as its proximity to Gargantua causes severe gravitational time dilation. The crew find an ocean world dominated by massive tidal waves, generated due to the immense gravitational pull of the black hole. With Miller dead, Amelia attempts to recover her data when one of the waves hits, killing Doyle and waterlogging the lander's engines, delaying their departure. By the time Cooper and Amelia return to Endurance, 23 years have passed on Earth.
The now adult Murphy works for NASA, assisting Brand with his equation to harness gravity. [clarification needed What equation? What does it do?] Before dying, Brand admits to her that he solved the equation long ago and deemed it impossible, lying to the NASA team to keep their hopes alive while their work on Endurance allowed for "Plan B". Murphy keeps working on the problem, concluding the equation could be balanced if more information from Gargantua's singularity could be retrieved. Low on fuel, Endurance can only visit one more planet before returning to Earth. Amelia suggests Edmund's planet, however the rest of the team chooses Mann as he is still transmitting and Cooper suspects that Amelia is motivated by her feelings for Edmund. Upon their arrival, Mann tells them the lower surface of the planet is habitable, but then lures Cooper away and reveals the planet is actually frozen and has a poisonous atmosphere. Driven to despair from loneliness and looming death, he falsified data about his planet's viability in hopes of being rescued. Mann, fearing the failure of the mission, cracks Cooper's visor and leaves him to die while planning to take command of Endurance to continue the mission. Meanwhile, Romilly discovers Mann's data was flawed but is killed by a bomb Mann planted to hide his secret.
Amelia rescues Cooper using a cargo ship and they return to Endurance, where they witness Mann attempting to dock imperfectly. The airlock depressurises, killing Mann and causing severe damage to Endurance. As it spins tumultuously toward the planet, Cooper manages to stabilise the vessel; however, the explosion has caused it to slip further into Gargantua's gravity well. Using the black hole's gravity as a slingshot, they plot a course to Edmunds, while another 51 years pass on Earth. Cooper and TARS detach their shuttles into the black hole in an attempt to collect data from the singularity, while reducing the ship's mass. Inside the black hole, Cooper descends into a tesseract: five-dimensional space created by a future human civilisation, compressed into a three-dimensional structure. Cooper ascertains gravity can be exerted across dimensions of space and time to communicate, and relays data on the black hole from TARS in a Morse code message by manipulating the second hand of a watch he gave to Murphy before he left. Murphy retrieves the watch on Earth and realizes what Cooper is doing, and solves the equation.
After Cooper is finished, the tesseract collapses, and he finds himself travelling back through the wormhole which results with Amelia shaking his hand. He awakens aboard a space habitat orbiting Saturn and reunites with Murphy, now elderly and on her deathbed after having led humanity's exodus. Satisfied that Cooper has kept his promise to return, she convinces him to leave and find Amelia. He takes TARS with him in a NASA shuttle, and heads through the wormhole toward Edmunds' planet, where Amelia and CASE have found Edmunds' wreckage. They set up base camp, finding the planet suitable for human settlement, and begin executing "Plan B".