Two years after Solomon Lane’s capture, the remnants of his organization, the Syndicate, have reorganized as a terrorist group called the Apostles. IMF agent Ethan Hunt while hiding in a safe house in Belfast, is assigned to buy three stolen plutonium cores in Berlin from Eastern European gangsters before the Apostles can. He is joined by Benji Dunn and Luther Stickell for the mission, but the team fails when Stickell is taken hostage and Hunt’s attempt to save him allows the Apostles to make off with the plutonium. The team later captures nuclear weapons expert Nils Delbruuk, whose security clearance was revoked because of his anti-religious bigotry and who designed nuclear bombs for the Apostles’ client, an extremist named John Lark. With the use of a broadcast of Dunn posing as Wolf Blitzer, they manage to trick him into handing over a phone that he used to communicate with Lark.
Furious at the IMF’s failure to secure the plutonium, CIA Director Erika Sloane instructs Special Activities Division operative August Walker to shadow Hunt as he attempts to retrieve it. Hunt and Walker infiltrate a nightclub party in Paris where Lark is believed to be buying the cores from arms dealer Alanna Mitsopolis, also known as the White Widow, who acts as the middleman in the sale of the plutonium. They track a man whom they suspect to be Lark, but after fighting him in a restroom, he is killed by MI6 agent Ilsa Faust. Hunt sticks to his plan, assumes the role of Lark without a disguise, and escapes from the hitmen sent to kill Lark and Mitsopolis.
To secure the plutonium, Mitsopolis tasks Hunt with extracting Lane from an armored convoy moving through Paris. She provides one of the plutonium cores as a down payment. With Mitsopolis and her brother Zola intending to use lethal force on local police, Hunt and Walker preemptively attack the convoy. Ramming Lane’s vehicle into water, they lead the police and Mitsopolis’s men on a chase across Paris while Dunn and Stickell, in a watercraft, secure Lane. Faust reappears and attempts to kill Lane to prove her loyalty to MI6, but the extraction is successful. Mitsopolis instructs the team to deliver Lane and Faust to London.
At a safe house in London, IMF Secretary Alan Hunley confronts Hunt, convinced he is the real John Lark, using evidence that has been doctored by Walker and passed to Sloane, but Hunt denies it. Eventually, Hunt, the team, and Hunley trick Walker into admitting he is the real Lark and informs Sloane, who sends in a CIA unit to take everyone into custody for transfer to Washington, D.C. However, the unit has been infiltrated by the Apostles, and Walker orders the infiltrators to attack instead. Walker kills Hunley and escapes after Hunt chases him across the city. As he departs for India with Lane, Walker tells Hunt he knows the location of Hunt’s ex-wife Julia and threatens her life should Hunt follow him.
The team deduces that Lane and Walker plan to detonate the remaining bombs at a medical camp over the Siachen Glacier, contaminating the water supply of India, Pakistan, and China; with a third of its population affected, the world will descend into an anarchy from which Lane and Walker hope a new world order will emerge. Upon arrival in Kashmir, Hunt discovers Julia and her new husband Erik are assigned to the medical camp, an arrangement made by Walker to increase the pressure on Hunt. Lane programs the bombs’ detonator with a 15-minute countdown and gives it to Walker, choosing to remain behind with the two nuclear bombs; Walker then takes off, secretly pursued by Hunt while Dunn, Stickell, and Faust stay behind to find and defuse the nuclear weapons. Stickell works to deactivate the first bomb and Julia volunteers her help, but they are unable to defuse it without the detonator. Dunn and Faust find the second bomb and subdue Lane. Following an aerial chase, Hunt uses a commandeered helicopter to ram Walker’s helicopter out of the sky and drops the helicopter’s winch hook on Walker’s head as they fight on a cliff, killing him instantly. Hunt then secures the detonator, allowing Stickell, Faust, and Dunn to deactivate the bombs.
In the aftermath, the remaining cores are safely recovered. Sloane hands Lane over to MI6 through Mitsopolis, with Faust earning her exoneration from the organization as a result. Julia tells Hunt that he has given her the best life, despite his commitment to the IMF. Faust and the team join Hunt in celebration.