DMZ, North Korea; The G.I. Joes are infiltrating a military base. Duke (Channing Tatum), Roadblock (Dwayne Johnson), and Flint (DJ Cotrona) go sneaking in while Lady Jaye (Adrianne Palicki) is keeping an eye out and Mouse (Joseph Mazzello) is their sniper. Mouse shoots the coffee mug of one soldier to cause a diversion. Suddenly, Roadblock is alerted and surprised to see a flag of the Joes standing at the base.There's a brief narration explaining how the Joes caught Cobra Commander and Destro (in the previous film), and they are now locked in a maximum security prison. Duke is the captain leading Roadblock, Flint, Jaye, and the masked mute Snake Eyes (Ray Park). However, Storm Shadow (Byung-hun Lee) and Zartan (Arnold Vosloo) are still at large. (Note: no mention is made of the Baroness whom is presumed to be still incarierated.)Sometime later, Duke and Roadblock are playing video games at the latter's home. Duke gets jumped by Roadblock's two daughters. The men see on television that the Pakistani president has been assassinated.The President of the United States (Jonathan Pryce, but really, Zartan still in disguise) meets with his men and has the choice to wait it out or head right in. He makes the decision to send the Joes out to Pakistan to obtain nuclear weapons.The Joes go down to the base in Pakistan where they are keeping the weapons. They start shooting at the bad guys and eventually get the weapons and disable them. Duke contacts the White House to confirm this.Zartan goes into an underground facility where they are hiding the real President. He taunts him and shows off the nanomites that keep his disguise together. He claims that the people of America are more fond of the way he is running the country with his eagerness to blow things up.Duke and Roadblock share a bonding moment where they make a bet on who can shoot a cupcake on a stand. Roadblock wins because he distracts Duke and brings out his own big-ass gun. Suddenly, the men notice jets coming in, thinking it's security. The jets start shooting down on the Joes and dropping bombs. The team scrambles for protection while firing back. Duke jumps in to save Flint, but he is killed in an explosion. Roadblock, Flint, and Jaye hide in a well and manage to fool the villains.The next morning, as the trio try to get out of the well, Zartan (as the President) addresses the nation regarding the attack. He frames the Joes for the attack in Pakistan and frames Snake Eyes for the assassination of the Pakistani president. The surviving Joes find that all of their guys are dead. Roadblock takes the dog tag off Duke's corpse.At the maximum security prison, Snake Eyes is being taken in. He is greeted by Warden James (Walton Goggins) and is brought down underground where it is shown that Cobra Commander (Luke Bracey) and Destro are being contained. They are in a tube filled with materials that paralyze every part of their body but keep their hearts and eyes functioning. James boasts "Welcome to hell" and Snake Eyes responds boastfully. His mask is removed, and it is really Storm Shadow underneath.A Cobra mercenary known as Firefly (Ray Stevenson) comes by the facility and sets out little explosive fireflies to break into the place. As this is happening, Storm Shadow makes his heart stop to alert the guards after he's been placed in the chamber. He manages to break out and kill most of the guards. He breaks Cobra Commander from his chamber, but they leave Destro, saying he is out of the band. They meet with Firefly, who comes in as James shoots a gas chamber, causing an explosion. James is killed by the Commander and the explosion's flames severely burn Storm Shadow's back.The villains go to an industrial complex where a large weapon known as Zeus is being constructed. Zartan comes in and informs the Commander about the three surviving Joes. Firefly says they'll be taken care of.Roadblock, Flint, and Jaye drop by Roadblock's old neighborhood. They take shelter in an old gym/arcade that he used to come by.In Tokyo, Japan, the real Snake Eyes meets with his mentor, Blind Master (RZA), and a Joe ally, Jinx (Elodie Yung). Blind Master tells them they must find Storm Shadow and get him to reveal Cobra's plans.Lady Jaye does some observations with the President's speech pattern and mannerisms to deduce that someone is impersonating him. Flint asks Roadblock who they can trust now, and he responds there is one man he knows.The trio go to the home of General Joe Colton (Bruce Willis), the original G.I. Joe. Roadblock explains the situation after showing Colton the dog tags of their fallen brothers. Together, they come up with a plan to prove that the President is a phony.Jaye goes out as a jogger and gets the attention of a man on the President's detail. She tricks him into helping her out with groceries, and Roadblock gets him to find them a way to the President.Somewhere in the mountains, Snake Eyes and Jinx have located the place where Storm Shadow is being treated. He is healed up by an old woman, and they notice that several ninjas are falling from great heights. Snake Eyes and Storm Shadow bitterly reunite and engage in a fight, while Jinx fights the old woman. She and Storm Shadow are neutralized, but the ninjas go after Snake Eyes and Jinx. Snake Eyes gets rid of them by causing an avalanche that sends the ninjas off the mountain to their deaths.At a gala that Zartan is attending, Jaye goes in disguised as a member of the President's detail. She gets in with a sexy red dress and gets Zartan's attention. One of his men, another Cobra ally, is suspicious and starts to do a scan on Jaye's face. She gets out after getting a hair sample from Zartan's coat and sends it to Roadblock. After scanning the sample, they learn Zartan's identity, just as Firefly comes in and tries to attack. He fights Roadblock and almost kills him until Flint and Jaye come by and ram him with their truck. Firefly gets out in time.Back in Tokyo, Storm Shadow is questioned by Blind Master, who hands him his sword. In this moment, it is revealed that, as a child, it was not Storm Shadow who killed his and Snake Eyes' master, but it was Zartan in disguise as a man who would mentor Storm Shadow into the assassin he became. He gives them the information they want.Firefly is beating the President up in the underground chamber. Cobra Commander comes in with a briefcase that would activate the Zeus weapon and scans the President's eye.In the gym/arcade, Snake Eyes, Jinx, and Storm Shadow come across the Joes, who are initially suspicious, but they join forces. They go back to Colton's place and meet with some of Colton's men to come up with a plan to stop Cobra's plans. Colton shows them his HUGE collection of weapons all over the kitchen and they start preparing.At Fort Sumter, Zartan meets with the other world leaders. At the same time, the Joes and Colton's men come in, taking out Cobra allies and other men. Zartan tells the world leaders to give up their nuclear weapons, but they say he has gone mad. He releases America's nukes into the air and detonates them as they are high above the sky. The other world leaders follow suit. Cobra Commander comes in with the Zeus briefcase, and it is revealed that Zeus is a series of satellites containing powerful rods. They drop one rod down onto London, almost completely destroying it, and sending the other world leaders into a frenzy. By this point, Cobra has officially taken over the White House. Storm Shadow and Jinx begin drawing their blades and start attacking. The Commander tells Firefly to be wary of the briefcase.Roadblock comes in on a large tank shooting the other villains' tanks while Jaye and Colton go retrieve the President. After shooting their way through dozens of goons, the duo find the underground chamber as one Cobra ally holds the President at gunpoint. Jaye shoots the President in the arm and Colton kills the goon.Flint goes in pursuit of Cobra Commander, but he escapes on a helicopter, just as his men are preparing for the other Zeus rods to hit other major cities around the world. Roadblock finds that Firefly is holding the briefcase. He nearly escapes on a motorboat, but Roadblock rams into it with another one. He and Firefly begin fighting again, but Roadblock manages to defeat him. At the very last second, he overrides the sequence and causes all the Zeus satellites to explode.Somewhere underground, after having escaped other ninjas, Storm Shadow finds Zartan pointing a gun at him. He tells Zartan he made him what he has become, and Zartan pulls the trigger, but Storm Shadow slices the bullet in half with his blade and throws it into Zartan's chest. As he dies, the nanomites wear off, and his real face is visible.Roadblock is walking away from the scene, but Firefly is about to set one of his firefly bombs on him. He reaches into his pocket for his detonator, but Roadblock is holding it. With the push of a button, the firefly explodes, and Firefly is killed. The Joes walk together triumphantly while Storm Shadow respectfully acknowledges Snake Eyes and walks away.The real President is put back into power and addresses the nation at a ceremony where Roadblock, Jaye, Flint, Jinx, and Snake Eyes are commemorated as heroes. Colton thanks each of them, but when he gets to Roadblock, he presents him with the gun of General Patton, so that when they finally catch Cobra Commander, they will be ready. Roadblock proudly raises the gun in the air and lets out one shot.