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After intercepting nerve gas being sold to Chechen terrorists in Minsk, Belarus, Impossible Missions Force (IMF) agent Ethan Huntis convinced he can prove the existence of the Syndicate, an international criminal consortium that the Central Intelligence Agency(CIA) does not believe exists. Hunt is captured by the Syndicate, but escapes a torture chamber led by Syndicate member Janik "Bone Doctor" Vinter with the help of disavowed MI6 agent and Syndicate operative Ilsa Faust.
CIA Director Alan Hunley and IMF Field Operations Director William Brandt testify before a Senate committee. The IMF, currently without a secretary in charge, is controversial because of its destructive methods and various misconducts. Hunley succeeds in having the IMF disbanded and absorbed into the CIA. Brandt, knowing that Hunley will try to capture Hunt, warns him to stay undercover. Cut off from the IMF, Hunt follows his only lead: a blonde man in glasses, later identified as former MI6 agent Solomon Lane.
Six months later, Hunt remains a fugitive. He enlists former colleague Benji Dunn to attend an opera in Vienna. He predicts that an attempt will be made on the Austrian Chancellor at the performance, and believes that Lane will also be there. He and Dunn stop three snipers including Faust, but the Chancellor is killed by a car bomb, and Lane is still not found. Faust drops hints of Lane's plan to Hunt before leaving. Dunn decides to stay with Hunt instead of reporting back to the CIA, despite knowing his action amounts to treason.
Hunt, blamed for the Chancellor's death, is pursued by the CIA's Special Activities Division. Learning of this, Brandt contacts Luther Stickell to find Hunt before the CIA does. Stickell tracks Hunt, Dunn, and Faust to Casablanca, Morocco. Here, the group plans to acquire a list of Syndicate agents, contained in a secure building. After they retrieve the data, Faust flees with it, evading both Hunt and Syndicate members. Hunt kills the pursuing Syndicate members, but Faust escapes with the data. Dunn reveals he copied the data onto a USB drive, as Stickell and Brandt catch up to Hunt and Dunn.
Faust returns to London and attempts to use the file to quit her mission to infiltrate the Syndicate, but her MI6 handler, Atlee, compels her to continue. She and Lane learn that Atlee wiped the drive. Meanwhile, Ethan learns that the data is actually an encrypted British-government red box that requires the Prime Minister's biometrics to unlock it. Lane's men abduct Dunn, and use Dunn and Faust to blackmail Hunt into decrypting the data and deliver it to them. Hunt agrees to the ultimatum, despite protests from Brandt.
As part of Hunt's plan, Brandt reveals their location to Hunley. At a London charity auction, Hunley, Brandt, and Atlee take the Prime Minister to a secure room to protect him from Hunt. Atlee reveals himself as a disguised Hunt and has the Prime Minister confirm the existence of the Syndicate, a proposed project to perform missions without oversight, making the Prime Minister an executioner with zero accountability. When the real Atlee arrives, Hunt forces him to admit that he began the Syndicate without permission. Atlee admits he has been covering up its existence after Lane hijacked the project and went rogue, turning the Syndicate against him and MI6.
With the Prime Minister's biometrics, Stickell decrypts the data and discovers the file actually contains access to 2.4 billion British pounds in various bank accounts. Hunt promptly destroys the data. At the meeting, he tells Lane he memorized the data, and offers himself in exchange for Dunn and Faust. Dunn escapes, while Ethan and Faust are chased through the streets of London by Lane's men. Faust kills Vinter in a knife fight, while Ethan confronts Lane and lures him into a bulletproof cell where he is gassed and taken into custody.
Hunley, having witnessed an IMF operation's success firsthand, returns with Brandt to the Senate committee meeting and convinces them to restore the IMF by covering for Hunt and his team. After the meeting, Brandt congratulates Hunley, who is now the new IMF Secretary.
