The story begins with a massive terrorist attack on the Brooklyn Bridge in New York. Explosives had been planted by Brotherhood agents, and nearly eight-hundred civilians perish as a result. In Times Square, a broadcast of Magneto's latest address to humanity is shown as he declares his return from his assumed death.
In Washington, D.C., Nick Fury meets with the President as they discuss Magneto's return. And in the Triskelion, the Wasp and Doctor Brankin watch the news feed on Thor and Iron Man responding to the fallout with search-and-rescue operations. Wasp mentions that Captain America, Hawkeye, and Black Widow left to follow a FBI tip about the Brotherhood extremists' location.
In New Jersey, the six Brotherhood mutants responsible for the Brooklyn Bridge attack are hiding out in a motel. The team includes Juggernaut, Mastermind, Toad, Rogue, Hard-Drive, and Vanisher. As they sit around, watching a news report of the attack, a smoke grenade abruptly appears in the room. Before the Brotherhood can react, Captain America crashes through a window and quickly disables Juggernaut, Mastermind, and Hard-Drive. Vanisher manages to teleport out, but the Ultimates have already anticipated this, and Black Widow quickly intercepts him, subduing the mutant.
The two remaining Brotherhood agents - Rogue and Toad - jump out of a window, but the jump breaks Toad's ankle. Hawkeye and S.H.I.E.L.D. agents surround them, but Rogue steals Toad's powers, using them to disable Hawkeye as she and Toad make a run for it. Unfortunately for them, Hawkeye manages to get back up and easily disabled the two fleeing terrorists with his arrows and marksmanship.
Back at the Triskelion and some time later, Quicksilver and Scarlet Witch meet with the rest of the team as they discuss tactics. Captain America outlines their objectives, stating that all Brotherhood mutants are being rounded up and that their main goal is to either capture or kill Magneto. He also states that so far they have failed to come into contact with the X-Men, and that Iron Man has been dispatched to investigate the Xavier Mansion.
At the Mansion, Iron Man finds the entire place abandoned. Meanwhile, Nick Fury has received new intel from the Pentagon and informs the entire team that the X-Men have allied themselves with the Brotherhood.
In the home of the Greys, Wasp visits Professor Grey. They have a dialogue where he tells her that he trusts Xavier, and that he doesn't know anything about the East Coast safehouse that they are reportedly hiding in. In the X-Men's New York safehouse, Professor X speaks to Moira MacTaggert over an intercom and mentions that Cyclops, Kitty, and Wolverine have yet to return from their Savage Land mission and that communication was lost. Colossus, Storm, Beast, and Jean get into an argument before the X-Jet suddenly returns. But only Kitty and Wolverine exit the jet, and Wolverine tells Jean that Cyclops is dead.
In the Triskelion, Captain America looks at an image of Wolverine and refers to him as Jim Howlett, stating that they served together back in WWII. He then mentions that Black Widow and Hawkeye busted a cyber-terrorist attack on the Stock Exchange, and notes that the Brotherhood will now be launching more attacks in the wake of Magneto's return. Stark then explains the mutant-location system he's devised, stating that he's updated Xavier's Cerebro tracker to locate mutants on a global scale. Scarlet Witch and Quicksilver add that all of the Brotherhood bases they were aware of have been vacated, but that there might have been a network of bases that Magneto never told them about. Suddenly, the power in the base goes off. The backup generator kicks in, but that power also goes down.
Magneto suddenly appears, tearing through the Triskelion's walls. He easily subdues Captain America and Thor. Quicksilver and Scarlet Witch are too fearful of their own father to attack, and after belittling his children, he then states that he will punish them for turning his Brotherhood into a 'stooge'. Using his powers, he shoots Quicksilver's kneecaps with two rifles. Magneto then tells Captain America that he has erased all Brotherhood intel from the Triskelion's drives. As Magneto leaves, a S.H.I.E.L.D. agent tells Cap that Xavier has managed to establish communication with the Triskelion in an attempt to broker a deal.
Captain America tells him that no deals will be made, and that the Ultimates will take the X-Men down along with the Brotherhood.
Somewhere in the U.S.A., Nick Fury brings the President to L.I.N.C.O.L.N. - the Leaders in Need Christian-Only Lockdown Network, a safe haven for every U.S. president since Lincoln's original assassination. The entire town is wired and its residents are all S.H.I.E.L.D. agents tasked with protecting the President from any Brotherhood attempts on his life. As Nick Fury and the President talk, Fury mentions that they've managed to keep Magneto's attack on the Triskelion out of the press and that record numbers of civilians are refusing to go to work in the wake of the Brotherhood reemergence. The President then asks Fury if he can guarantee bringing Xavier in alive (since the X-Men saved his daughter's life before), but Nick Fury says he can't promise this.
In the Triskelion, Captain America and Wasp are surveying Bruce Banner's destroyed cell. During the power outage, the Hulk managed to break out and devour all of the nursing staff before knockout gas disabled him. Captain America then tells Wasp that Fury has known about her mutation since she joined the team, and assures her that they are having a war of terror, not a war on mutants. On the news, reports state that a Brotherhood plot to destroy the Champs Elysees was foiled in Paris, and that Xavier has made a pledge to catch Magneto. In Cleveland, Ohio, Iceman watches the broadcast as he hides out with his father.
Back in the X-Men's safehouse, Xavier tells Jean Grey that he plans to negotiate a deal with Magneto. Jean tells the Professor that she suspects Wolverine might have let Cyclops die in order to get with her. Later, in the Metropolitan Museum of Art, Xavier (along with Kitty, Storm, and Jean ), meet with Magneto (who is accompanied by the psychic Unus to hide his identity). Xavier tells Magneto that he is willing to join forces with the Brotherhood, as long as they agree on an appropriate body count as to the execution of the United States and that their old mutant manifesto is used. He gives Magneto time to think about this, and as Magneto and Unus leaves, the entire ruse is revealed. Xavier was in actual fact, using the deal as bait for Wolverine to track Magneto back to his Brotherhood base (Wolverine's Weapon X conditioning protects his mind from telepaths and sensors).
But as Wolverine tracks them down, it is also revealed that Magneto already knew that Xavier was lying, and that he has leaked the location of the X-Men's safehouse to the authorities. Neuron scrambles are activated to prevent Xavier and Jean from using their telepathic powers, as the Ultimates move in to arrest the X-Men.
In Manhattan, Wolverine is ambushed by S.H.I.E.L.D. helicopters. Wolverine easily disables them all.
Back in the X-Men's safehouse, Iron Man (after bombarding the safehouse) flies to aid the S.H.I.E.L.D. agents with Wolverine. As the X-Men flee their compromised hideout, Colossus intercepts Iron Man, and begins beating him up. Storm cooks up some thunder, but she is defeated by Thor. Meanwhile, Beast escapes through the safehouse's training area, carrying the Professor on his back. Hawkeye tails them, but Beast activates the training program, forcing Hawkeye to fight against the computer's simulations. Beast and the Professor escape on an emergency plane, but Black Widow manages to hitchhike on it and disables the plane with some explosives. The two mutants eject from the plane, but Iron Man manages to snag their parachutes.
Suddenly, Wolverine lunges from the top of a building for Iron Man, causing him to crash-land as Xavier and Beast manage to break free. Wolverine then lands onto two S.H.I.E.L.D. troops who were trying to detain Jean and Kitty, and proceeds to tear them up before Captain America appears. Cap reveals that he knew Wolverine during the war, unlocking memories in Wolverine's mind and temporarily confusing him long enough for Captain America to defeat him with a rifle. Meanwhile, Colossus continues beating on Thor before Hawkeye fires a nuclear arrow at the mutant, disabling him.
Before a S.H.I.E.L.D. sharpshooter can disable Xavier and Beast, Iceman suddenly appears, covering the entire area with a swath of ice, disabling the Ultimates' neural scramblers. Xavier then shuts down every non-mutant mind, buying some time for his students to escape. However, they don't know that Wasp is a mutant, and she manages to sting Xavier, disabling his telepathic assault. Unfortunately, the X-Men have still managed to escape, and only Xavier is detained.
At the Triskelion, Magneto secretly appears in Xavier's cell and reveals that he was the one who engineered the entire conflict. He tells Xavier that the reason for his plan was to bring the X-Men into the Brotherhood.