Mitchell's first assignment with Atlas is to rescue the Nigerian Prime Minister, Samuel Abidoyo, from the KVA, a large anti-western, anti-technology terrorist organization. The president and a few other technologists are held hostage at a technology summit in Lagos but is quickly rescued by Atlas forces, who soon discover that the KVA are not targeting the president, but a technologist who was attending the conference. They pursue the escaping KVA vehicles and recover the technologist, who is taken back to Atlas HQ on Irons' orders.
Soon afterwards, the KVA launches a massive surprise attack on nuclear power stations all over the world. Mitchell, along with a massive Atlas quick-reaction force, is sent to retake a power plant in Seattle, Washington, and although the Atlas forces manage to defeat the KVA, they are too late to stop the KVA from initiating a meltdown and blowing up the reactors. 50,000 people around the world die as a result of the KVA attacks.
Four years later, the world has recovered from the attacks with the help of Atlas, which has provided aid and shelter to everyone affected. Atlas has now become the largest corporation in the world and effectively controls much of the world's resources. Mitchell, Gideon and Joker are stationed in Detroit to track down an affiliate of the KVA, Dr. Pierre Danois, who has information on the whereabouts of the KVA's leader, codenamed Hades. They track down Danois successfully and he is interrogated by Ilona, who manages to get answers out of him.
Danois' intel points to Hades being in Greece, and Irons sends Atlas forces to track him down and kill him, despite opposition from U.S. officials. Mitchell and Ilona locate Hades and Mitchell shoots him using a WASP drone, but it is revealed to be a double. The double is rigged with explosives that go off after his death and almost wipes out the squad if not for a sacrifice made by an Atlas operative. The compound is soon swarmed by other KVA operatives and the remaining Atlas forces must fight their way out. The real Hades makes an attempt to escape, but Mitchell and Ilona stop him and, after a brief struggle, Mitchell cuts Hades' throat. As he is dying, Hades utters the words "Irons knows" and gives Mitchell and Ilona a storage device containing a recording.
With Atlas now at the height of their popularity due to killing Hades and effectively destroying the whole of the KVA, Mitchell and Gideon are accompanying Irons at the Atlas headquarters in the thriving New Baghdad. Ilona shows Mitchell and Gideon the recording that Hades gave them, and it reveals that the technologist from Nigeria warned Irons of the KVA attacks on the nuclear reactors, but Irons killed the technologist and deliberately kept quiet about the attacks in order to make a profit from the aftermath. Gideon believes the recording is a fake, but Mitchell and Ilona attempt to flee the headquarters, only to be held captive by Atlas troops on Irons' orders. They are contacted by an unknown person who assists them in escaping captivity, and they escape New Baghdad. Their unknown assistant turns out to be Mitchell's old sergeant Cormack, who is now part of an elite U.S.-led multinational team known as the Sentinel Task Force, whose priority was previously to investigate the KVA attacks and prevent anything like it from happening again, but once Atlas and Jonathan Irons grew in power, it became clear he and his company were the bigger threat, and the Sentinels are now investigating Irons and Atlas.
Mitchell and Ilona defect to Sentinel and, along with Cormack and Knox, infiltrate Irons' home in Bangkok to find intel on a mysterious Atlas operation called "Manticore". They find out that "Manticore" is a biological agent that only targets specific genotypes (those that are not registered on the Atlas database) and will not affect any Atlas personnel, meaning Irons can deploy it in the midst of a battle without risking harm to his own troops, while the opposing force is annihilated . They tag a cargo plane that is about to transport a large shipment of Manticore before pulling out.
Later, the Sentinel forces move in on the Atlas cargo plane and bring it down over Antarctica. As they are attempting to secure the Manticore, a large Atlas force ambushes from drop pods and recovers the Manticore. Cormack, Ilona and Mitchell manage to take out most of the Atlas soldiers, but are captured by Gideon and his squad. Gideon calls for evac before suddenly shooting his squadmates and helping the remaining Sentinel forces dispose of the Manticore.
With Gideon now on the side of Sentinel, he is reunited with his old teammates once more. Gideon reveals where Manticore is being made - in an Atlas bio lab in Bulgaria. He and Mitchell infiltrate the lab and destroy it before escaping in an experimental Atlas hover-tank.
A month later, Jonathan Irons is inaugurated into the United Nations. He issues a speech effectively declaring war on the governments of the world, now obsessed with total domination and believing the world would be better off under Atlas. His first move is an attack on the Golden Gate Bridge in San Francisco, which Sentinel forces attempt to repel. They fail, and the Golden Gate Bridge is demolished over a U.S. Navy carrier, which is promptly boarded by Atlas forces. Mitchell and Gideon are among only a handful of Sentinel operatives to survive the attack, and are soon joined by Cormack and Knox, who help them in retaking the carrier and destroying the advancing Atlas ships.
With Atlas now officially at war with the world, U.S. forces close in on the Atlas headquarters in New Baghdad. Mitchell, Ilona, Cormack, Gideon, and Knox are among the personnel involved in the attack, and they manage to defeat most of the Atlas forces in the area. With New Baghdad under siege and Atlas losing, Irons deploys Manticore, which wipes out all the U.S. forces in the area, including Knox. Mitchell, Ilona and Gideon survive since they were once Atlas personnel and are thus unaffected by Manticore.
The three are captured and taken to an Atlas prison camp, where they meet up with Cormack. Irons meet the four in person and shoots Cormack in the leg before destroying Mitchell's prosthetic arm as payback for him defecting from Atlas. Ilona and Gideon overpower their captors and rescue Mitchell and Cormack. Whilst escaping, they learn that Irons plans to unleash Manticore strikes on military bases all over the world. They escape the camp after Mitchell commandeers an AST, but Cormack succumbs to his wounds and dies.
With little hope of taking New Baghdad and stopping Atlas, Mitchell and Gideon attempt one final, all out frontal attack in a pair of AST suits, while Ilona guides them. They manage to infiltrate the Atlas launch center and destroy the Manticore rockets before they are launched. However, because they had to access the rocket from the launch vents and they were caught in the blast, Mitchell is in critical health, so Gideon has to carry him. Irons shows up and locks down their exoskeletons, rendering them unable to move, but refuses to kill them in an attempt to show that he still has some humanity left in him, still claiming that he was "saving the world from itself." and Gideon arguing "Twisted fucks throughout history have used the same argument...". As he flees, Mitchell manages to escape his exoskeleton and catch up with Irons in his office at the top of the Atlas headquarters. After a brief struggle, Irons nearly falls off the edge of the roof, but grabs onto Mitchell's lifeless prosthetic arm and tries to convince him to pull him up to safety. Mitchell, unable to shake Irons off, severs his own prosthetic arm with a knife and watches as Irons falls to his death. As Gideon arrives to help Mitchell, he comments that Atlas is still at large and the war has only just begun.