Bond and field agent Eve assist on a mission in Turkey in which an MI6 operative has been killed and a hard drive stolen. The drive contained details of all NATO agents operating undercover in terrorist organisations. Bond and Eve chase the assailant, and attempt to recover the disk. During the chase, Bond is shot in the shoulder, but continues his pursuit, until he is shot from a train by Eve, who misjudged her shot. He is posted as "presumed killed" but survived actually, starting to live a life far from his duties, a life filled with sex and alcohol in a remote and sunny country.

Five of the agents' names are released onto the internet, with the promise of more the next week, and M comes under political pressure to retire during a meeting with the Chairman of the Intelligence and Security Committee, Gareth Mallory. On her return from the meeting, MI6 is hacked and an explosion occurs in the offices, killing a number of MI6 employees. On hearing the news of the attack, Bond returns to London. He is given a palmprint activation PPK/S by the new Quartermaster. Shrapnels taken from his shoulder help the MI6 to identify the man who used them, Patrice, and Bond is sent to Shanghai, where it is known the mercenary will shortly arrive.

Bond finds and follows the mercenary and witnesses him undertake an assassination, at which Bond also sees Severine. The two men fight, and Patrice falls to his death before Bond can find out who his employer was. Searching the assassin's equipment, Bond finds a gambling chip, which leads him to a casino, where he is paid €4million for the kill. Severine warns Bond that he is about to be killed, but promises to help him if he will kill her employer. Bond beats his attackers —with help from Eve— and joins Severine on her boat, the SY Regina. They travel to an island but are taken prisoner by the crew and delivered to Severine's employer, Raoul Silva. Silva had previously worked for MI6 and blamed M for his capture, torture and imprisonment by the Chinese. Silva kills Severine in a William Tell-esque game, but Bond overpowers his guards and captures Silva with the help of a helicopter raid.

Back in the MI6 headquarters, Q attempts to decrypt Silva's laptop, but instead of accessing the computer successfully, the computer has been programmed to access the MI6 computer system and release Silva, enabling him to escape into the London Underground tunnel system. Pursued by Bond, Silva uses the disguise of a policeman and attacks M during a public enquiry into her handling of the stolen hard drive. Bond arrives to join Mallory and Eve in beating off Silva's attack, and M is hurried from the building by her aide, Bill Tanner. Bond drives M and her car away from the scene and, after exchanging it for his own Aston Martin DB5, drives her to his empty and remote childhood home in Scotland, Skyfall. He instructs Q to leave an electronic trail for Silva to follow, a decision supported by Mallory.

At Skyfall, Bond and M are met by Kincade, the gamekeeper of the Bond family estate. The trio are only lightly armed with hunting shotguns, dynamite, knives and gas bottles, but they improvise a series of booby traps. When Silva arrives, Bond, M, and Kincade fight off the first assault, making good use of the Aston Martin's front machine guns (for the first time in the series) in the process, although M is wounded by Silva's men. Silva arrives by helicopter with a second wave, and Bond sends M and Kincade off through a tunnel at the back of a priest hole to a chapel on the grounds near the grave of Bond's parents. The second assault consists of firepower from the helicopter, with Silva throwing incendiary grenades into the building. The Aston Martin is destroyed. Bond detonates a stick of dynamite with two gas bottles and retreats down the tunnel. The resulting blast causes the helicopter to crash, killing a number of Silva's men. Silva sees Kincade's torch beam, follows and arrives at a frozen lake ahead of Bond. Bond attacks Silva's sole remaining follower, and the two fall through the ice, where Bond kills him. In the meantime, Silva makes his way to the chapel and forces his gun into M's hand where he begs her to kill them both. Bond arrives and throws his knife into Silva's back, but M collapses from her wound and dies. Bond inherits M's porcelain Union Jack bulldog after her funeral.

The MI6 headquarters are moved to the Universal Exports building (from the earlier films), while Eve decides not to return to the field as an agent. She reveals her full name to Bond : Eve Moneypenny. A newly appointed M is waiting for Bond in his office : Gareth Mallory.