Ethan Hunt and his team, consisting of William Brandt, Benji Dunn, and Luther Stickell, are attempting to retrieve a package aboard a cargo plane that is about to take off in Minsk, Belarus. Luther connects Benji to the satellite, which allows him to hack into the electronics of the plane. However, most of the plane's systems is secured, and he cannot shut down the fuel pumps, hydraulics, or the electrical system. Ethan leaps onto the plane and tells Benji to open the door, but only ends up opening the cargo door. Benji eventually gets the right door open and Ethan escapes the plane with the package through the cargo door.
Sometime later, Ethan discovers that the package on the plane was a nerve gas being sold to terrorists, but none of the people who had sent the gas from Belarus had the means to obtain it. Ethan is convinced that he can be led to the Syndicate, a terrorist organization whose existence has been in doubt. While at a record shop in London to receive his next mission, he finds out that he has been led into a trap by the Syndicate and is forced to watch as a man in glasses kills his contact before passing out from sleeping gas. Ethan later wakes up and is tortured and beaten by Janik Vinter, who's also called the "Bone Doctor". Ethan manages to escape with the help of disavowed MI6 agent Ilsa Faust, but she refuses to go with him.
The CIA director, Alan Hunley, and William Brandt appear before a Senate committee, and since the IMF has no secretary and is controversial due to their destructive methods, Hunley has the IMF disbanded and aborted. This guarantees Hunley that with the IMF's dissolution, Ethan will soon be captured within the day as Hunley assumes that Ethan had gone rogue. Brandt warns Ethan to stay undercover, telling him that Hunley will stop at nothing to catch Ethan. Ethan finds that his only lead to the Syndicate was the blonde man in glasses, who he assumes to be the leader, a former MI6 agent named Solomon Lane.
Six months later, Ethan is on the run from the CIA and enlists the help of his friend Benji to help find the Syndicate and its members. Ethan invites Benji to Turandot in Vienna, in order to search for Lane. At the opera, they discover that the Austrian chancellor is attending the show, and attempt to thwart the assassination. Ethan and Benji prevent the snipers from killing the chancellor, one of the snipers being Ilsa, but he is later killed by a car bomb. Ethan later reveals to Benji what the Syndicate's purposes are. While they have been assassinating minor world leaders, the chancellor's murder shows signs that they are beginning to reveal themselves to the public. Convinced Ethan was involved in the assassination of the chancellor, Hunley authorises his forces to kill them.
To save Ethan from Hunley, Brandt recruits Luther to find Ethan before Hunley's team does. Brandt and Luther track Ethan, Benji, and Ilsa to Morocco, where the three plan on infiltrating a server to find a well-protected ledger that contains the names of all Syndicate agents as well as information as to where the Syndicate gets its money. During the heist, Ethan nearly drowns but is saved by Ilsa, who revives Ethan. However, Ilsa knocks Benji unconscious shortly after reviving Ethan and flees with the data. Ethan and Benji chase after Ilsa with the Syndicate agents hot on their tail, during which they run into Brandt and Luther. While Ilsa escapes, Benji reveals to Ethan that he has a copy of the data.
Ilsa returns to London and meets with her handler, MI6 director Atlee, and Atlee tells Ilsa to continue with her mission and go to Lane. When she meets with Lane, she finds that Atlee had wiped out the drive. The drive is revealed to be an encrypted red box, which can only be unlocked by the Prime Minister. When Ethan and his team confront Ilsa, Benji is suddenly kidnapped by Lane, and Lane tells Ethan that he must deliver a decrypted copy of the data to Lane by midnight tonight. Ethan complies.
At a charity audition, Atlee, Brandt, and Hunley escort the Prime Minister to protect him from Ethan. Ethan, having disguised himself as Atlee, reveals himself then forces the Prime Minister to reveal the Syndicate's existence. The real Atlee soon arrives, but Ethan and Brandt subdue him and his guards and forces Atlee to reveal the truth about the Syndicate. Atlee had created the Syndicate, but Lane went rogue and turned it against Atlee. As a result, Atlee had been covering up the Syndicate's existence.
Luther discovers that the drive contains access to billions of pounds, and warns Ethan that if Lane gets his hands on the money, they will be unleashing a "terrorist superpower". Ethan memorizes the data then destroys it before arriving at the meeting point outside the Tower of London. Once there, he discovers Benji strapped to a time bomb and Ilsa holding him at gunpoint. Lane talks through Benji, demanding where the disc is. Ethan responds that he has the data memorized, and the only way Lane can get his hands on the money is for him to release Benji. Benji is soon released then Lane orders his men to kill Ilsa and take Ethan alive. A shootout soon occurs and Ethan and Ilsa are chased by Vinter and the Syndicate agents. Ethan and Ilsa fight their way through the Syndicate agents and Ilsa faces off against Vinter in a knife fight. Ilsa kills Vinter and Lane chases after Ethan. When Lane appears to have Ethan cornered, Lane is then trapped by Brandt and Luther in a bulletproof cell and is soon gassed by Benji. As Lane is taken into custody, the police arrive on the scene. Ethan and Ilsa embrace before Ilsa drives away, telling Ethan he knows where to find her.
Sometime later, Hunley and Brandt return to the Senate committee, and Hunley is convinced to restore the IMF. Hunley reinstates the IMF, claiming that having it disbanded was for Ethan to go undercover. The committee soon approves, and after the meeting, Brandt tells Hunley, "Welcome to the IMF, Mr. Secretary."