About 20 years before the story takes place, solar flares irradiate the Earth, killing over 99% of the world's population. The survivors gather in a network of safe cities and build primitive humanoid robots, called Pilgrims, to help rebuild and operate in the harsh environment. These robots have two unchangeable protocols: They cannot harm any form of life and may not repair, modify, or alter themselves or other robots in any way. Initially seen as humankind's salvation, they are relegated to manual labor when they fail to stop the advance of desertification. Society has regressed due to lack of technology besides the Pilgrims, as a lack of functional aircraft or other transport prevents travel and cars are a rare commodity, and humanity is on the brink of extinction. In 2044, Jacq Vaucan—an insurance investigator for ROC, the company that manufactures Pilgrims—investigates a report from Wallace, a police officer who shot a robot he claims was modifying itself. As Jacq looks for a robot they suspect was stealing parts, it leads him outside the city. When he finds it inside a shipping container, it sets itself on fire. As he and a team open up the burned robot to see what it was hiding, they discover the robot had a rare nuclear battery that could power a robot indefinitely. They are able to power up the robot once more, but when he asks it why it set itself on fire, it burns out again. Jacq salvages the remains and speculates to Robert, his boss and brother-in-law, that there may be a "clocksmith", someone who illegally modifies robots, who is overriding the second protocol. Incredulous, Robert rejects this possibility, but offers Jacq a transfer out of the city if he can find evidence. Jacq had asked for the transfer to a city on the coast, because he feared raising his unborn child in the decaying city, even though Robert is skeptical whether the ocean still exists. Jacq's pregnant wife, Rachel, initially rejects his plans, but she eventually relents. Jacq and Wallace investigate a brothel, where they find Cleo, a modified robot that Wallace subsequently shoots in the leg. When Jacq objects, Wallace says that Cleo's owner will lead them to the clocksmith; Wallace also threatens to kill Jacq if he does not split the proceeds of the battery on the black market. Jacq follows Cleo's owner to a clocksmith named Dr. Susan Dupré, who claims not to know who altered Cleo, an action that would destroy Cleo's CPU. Jacq leaves the burned robot's CPU with her and offers to give her the battery if she can locate information on the clocksmith. When Dupré installs the modified CPU in Cleo, Cleo begins self-repairing. Dupré contacts Jacq, who alerts Robert; however, ROC intercepts Jacq's message and sends a team of assassins to Dupré's laboratory. Dupré is killed, but Jacq escapes in a car driven by Cleo. When Cleo takes them into a maze of stanchions, both cars crash; the assassins are killed, and Jacq is injured. Cleo takes Jacq with her into the desert, where they are joined by three other robots, none of whom will obey Jacq's orders. However, the first protocol forces them to prevent his death. Desperate to return to the city to be with his pregnant wife, Jacq makes contact with Robert, who sends Wallace to recover him. Wallace threatens Jacq's life and destroys two of the robots, who have objected to his actions; Jacq kills Wallace with a flare gun before he can also destroy Cleo. Wallace's partner flees after taking a battery from one of the robots. Robert's boss discloses that the predecessor to the first Pilgrim was a quantum mind created with no security protocols and no artificial restraints on its computational power. Before they deactivated it, its makers tasked it with designing the security protocols that govern Pilgrims. Robert's boss informs Robert that no one has been able to break Pilgrim security protocols, because they were created by the unrestricted quantum mind and ROC purposefully limited the computational power of all subsequent AI. ROC forces Robert to accompany a team sent to kill Jacq and the unknown clocksmith before the robots can evolve further beyond human understanding. When Robert objects to their kidnapping Jacq's wife and baby daughter, Conway, the leader, shoots him and leaves him for dead. Meanwhile, Jacq meets the robot responsible for modifying the others. The robot says that he and the other robots plan to go to the radioactive area where humans cannot go. Initially skeptical, Jacq eventually accepts that the robot naturally evolved, like humanity. The robot cannot understand why Jacq is afraid of dying, as death is a normal part of human living, just as the impending extinction of humanity is normal. "No lifeform can inhabit the planet eternally." It points out that the androids were conceived of and built by humans, so humanity will continue to exist through the robots that they created. Accepting this, Jacq gives them his battery, which they use to complete a new design, a sort of dog/insect robot. The robots repair a vehicle for Jacq, and he leaves for the city. When Conway reaches the robot outpost, he destroys two of the four robots. Jacq finds the dying Robert and returns to the outpost as Conway wounds Cleo and kills the evolved robot. Jacq kills all ROC assassins except for Conway, though he is further wounded in the battle. As Conway prepares to kill Jacq, the new robot saves his life by pushing Conway off a cliff in violation of the first protocol. Jacq fears the uninhibited robot will now attack him and prepares to shoot it, only to lower his weapon as his wife arrives with their child. He works the crane so Cleo and the new robot can cross to the other side of the canyon into the irradiated area. Jacq and his wife take a car and drive toward the city on the coast. Jacq appears to be dying of his injuries, but takes comfort in their child. As she drives Rachel suddenly breaks out into a smile and tells Jacq she can see the ocean ahead.

Dagny Taggart pilots an airplane in pursuit of another plane. Dagny asks herself, "Who is John Galt ?" before apparently crashing into a mountainside. Nine months earlier, Dagny is trying to understand the abandoned prototype of an advanced motor she and her lover Hank Rearden have found. Scientists across the country have been disappearing under mysterious circumstances, but Dagny is able to locate Quentin Daniels, who agrees to help from an abandoned laboratory in Utah. Dagny's brother James Taggart, president of the family railroad company, meets store clerk Cherryl Brooks and brings her to see a renowned pianist, who disappears during his performance, leaving a note asking, "Who is John Galt?" Later, at James and Cherryl's wedding, Dagny's friend Francisco d'Anconia argues with other guests about whether money is evil, and secretly informs Rearden about devastating explosions at his copper mine —the next day. Rearden spends the night with Dagny. Later, he is confronted about the affair by his wife Lillian, but when he offers a divorce she declines, in order to maintain her position in society. Rearden sells his advanced Rearden Metal to Ken Danagger's coal mining company, but refuses to sell it to the federal government, in defiance of the newly enacted "Fair Share" law that forces businesses to sell to all buyers. The two are charged under the law. Dagny barges into Danagger's office, realizes that he too is about to disappear, and understands that she is close to understanding the force behind the disappearances. At trial, Rearden defends individual freedom and the pursuit of profit, and is given only a token penalty by the court, which fears turning him into a martyr. The government announces "Directive 10-289", which freezes employment and production and requires that all patents be gifted to the government. Rearden defies this decree as well, but relents when he is blackmailed with photos of himself and Dagny that would damage Dagny's reputation. When Dagny hears about Rearden's "gift" and her brother's complicity, she quits the railroad. During her absence, a Taggart Transcontinental train collides with a military train in a tunnel, due largely to political pressure by a passenger and human error by Dagny's poorly trained replacement. This impels Dagny back to her job. D'Anconia tries to dissuade her from returning, as he had earlier tried to talk Rearden into leaving his business, but she returns anyway. Dagny takes a train to Colorado to show her faith in the railway, but its engine fails. The repair technician used to work for 20th Century Motor Company, which produced the motor Dagny found. He tells Dagny how the need-based reward system in his company failed, and his coworker John Galt left the company vowing to "stop the motor of the world". Dagny calls Daniels, who tells her that he is quitting. Dagny buys a small airplane and flies to Utah to try to dissuade him, but as she is landing, she sees him get into a plane on the airstrip. After a pursuit in the air—the opening scene of the film—Dagny's plane crashes in a valley hidden by stealth technology. A wounded Dagny Taggart crawls to the edge of her crashed plane, where she is greeted by John Galt. The film ends with a quote from Ayn Rand: "Money is the barometer of a society's virtue. But when you see that in order to produce it, you need to obtain permission from those who produce nothing... You will know that your society is doomed.

A prologue, set in the 12th century, where Rangarajan Nambi, a devout Vaishnavite, resists King Kulothunga II's efforts to desecrate a Vishnu idol. Nambi is executed by drowning, along with the idol, setting a thematic backdrop for the story. In 2004, Govindarajan Ramaswamy, an Indian scientist in the U.S., is working on a bio-weapon—a synthetic virus. When a lab monkey dies after ingesting the virus, Govind realizes the threat it poses. After discovering that his superior, Dr. Sethu, plans to sell the virus to terrorists, Govind flees with the vial. During a scuffle, the vial is mistakenly shipped to India. Christian Fletcher, a mercenary ex- CIA agent hired to retrieve the vial, kills several people in pursuit, including Govind's friend Suresh and his wife Yuka. Govind follows the package to Chidambaram, where it ends up with an elderly woman, Krishnaveni, who unknowingly hides it inside a Vishnu idol. Govind's attempts to retrieve it are complicated by Fletcher's pursuit, the local police, and Krishnaveni's devout granddaughter, Andal, who believes he is trying to steal the idol. Multiple subplots unfold: Fletcher's translator-wife and partner-in-crime, Jasmine, is killed during a skirmish involving a rogue elephant; Yukha's brother Shingen, a Japanese martial artist arrives to avenge Yuka's death; and Telugu police officer Balram Naidu investigates Govind's activities. Along the way, Govind and Andal encounter various characters, including social activist Vincent Poovaraghan and a Muslim family headed by the towering Khalifulla. The vial is accidentally switched with a medicine cooler belonging to singer Avatar Singh, who is being treated for throat cancer. Eventually, Fletcher takes hostages, demanding the virus in exchange. After a series of chases and confrontations—including one at Avatar's concert—the vial ends up back in the idol. Govind attempts to neutralize the virus by immersing it in the ocean after finding out that sodium chloride weakens it. A fight breaks out at a construction site between Govind and Fletcher, with Shingen intervening. Fletcher swallows the virus but dies as a massive tsunami hits the coast. The natural disaster wipes out the threat, killing Fletcher and causing widespread destruction. Govind, Andal, and others survive. Andal believes the tsunami was divine intervention, but Govind maintains a rationalist view, questioning the morality of such devastation as a means of salvation. They then profess their love for each other. Govind is honored for his efforts with an event, attended by world leaders, and a final glimpse of Nambi's idolized remains washed ashore.