The movie starts with a flashback to Charles Xavier and Cain Marko as teenagers. We see how Cain is beaten by his angry father while Charles is shown favoritism. We clearly see that Cain resents Charles for it. Then we fastforward to see (much like in the original X-men) a young Rogue kiss a boy and nearly kills him through touch. Distraught, she becomes a runaway when she meets Mystique. Mystique offers to help her adjust to her abilities and learn "how to put them to good use". Then finally we get to the present. Cain Marko is an adult now and a diamond smuggler in Africa. He searching through the jungle for the Crimson Gem of Cyttorak. Upon finding it in a temple, he reads the inscription on it. He then immediately transforms into the Juggernaut and is donned with armor and the helmet to protect his one vulnerability...his mind.
We see Rogue (who looks more dark and villainous) at a speech by Senator Kelly for more control on Mutants. Rogue makes her way through the crowd and gets closer to the stage. She pulls out a gun and points it at Senator Kelly. A blond lady wearing a bandana then sees Rogue and intervenes. Rogue gets a shot off but misses. The blond is revealed to be Ms. Marvel who was hiding in the crowd to keep the peace. Ms Marvel then says, "Sorry, looks like you're only gonna known as the WOULD BE assassin of Senator Kelly." to which Rogue replies, "I'm not an assassin, I'm a decoy." Ms. Marvel then looks back to see Senator Kelly is missing and abandons Rogue to find him. As his security staff is leading him away, one of the bodyguards pulls his gun and kills all the other members of the staff. He then points his gun at Kelly and reveals himself to be Mystique who finally has him alone. Ms. Marvel flies Senator Kelly to a safe distance and goes back to find Rogue and Mystique. Ms. Marvel spots them and attacks Mystique. In an attempt to save her, Rogue removes her gloves and grabs Ms. Marvel. Ms. Marvel, then tries to fly away but Rogue is still holding on but is now holding on in fear of falling to her death. Ms. Marvel is flying frantically in pain as Rogue continues to suck the life from her. Rogue is feeling overwhelmed by all the power she is absorbing causing her to get a white streak in her hair. They then fall and land in the East River. Mystique wants to search for them but she's injured and afraid to get caught so she transforms and goes into hiding.
The Juggernaut is raging through Africa as he begins to search for Professor X. He smashes through anything that stands in his way and makes it to a Cargo ship where he hides out and waits for it to reach the US. Meanwhile, Rogue and Ms. Marvel, unconscious, are found by Wolverine who decides to take them to the X Mansion. Wolverine isn't officially part of the X Men but it's the only place he think can help. Rogue wakes up in a clinic in the mansion and doesn't know what has happened (this scene practically mirrors the one where Wolverine wakes up in the original X Men movie). She is given a tour of the mansion and is introduced to what the X Men are and how they try to help mutants to cope with their abilities (they are unaware of her assassination attempt as Prof. X doesn't like to pry into people's minds without permission). Ms. Marvel was taken to a special hospital in Genosha because she has become braindead. Prof. X offers to help Rogue and invites her to join the school. She is then suddenly struck with a massive migrane. Prof. X manages to ease her mind and realizes what has happened. He decides to help her brain adapt to Ms. Marvel's mind (as he is unable to transfer it to her body).
The X Men then find out that a man called the Juggernaut is on a rampage heading towards the Mansion. The X Men are deployed to stop him while Prof. X continues to help Rogue. In their encounter with the Juggernaut, they are unsuccessful in stopping him and find out he is Cain Marko, Prof. X's step brother. They return and inform Prof. X who tries to use cerebro to help stop the Juggernaut but he is unable due to his helmet. Then we introduce Gambit. He and Rogue have some heart to heart as she struggles to understand her time with Mystique as a criminal. Gambit relates some of his experience with the his time as a criminal in the Bayou. Rogue confides in him about how she thinks her power is a curse and that he used to have the same problem with his Kinetic Energy. He also mentions how there are those who have it worse like Scott Summers (Cyclops) because he lost his ability to control his powers due to trauma he incurred during a plane crash as a child and how he will most likely never be able to control his optic blasts.
Prof. X declines moving for his safety as Rogue's condition worsens and he needs to help her. He continues to work on her mind in the danger room as they barricade the mansion and prepare for Juggernaut's coming. When they Juggernaut arrives, they all try to get his helmet off so Prof. X can stop him. They battle and the Juggernaut stomps through all of them while Prof. X finally heals Rogue's mind. As Juggernaut makes his way into the Danger Room, he pushes through the defenses but is surprised by Rogue (who now has Ms. Marvel's powers). Rogue manages to pull off Juggernaut's helmet with her super-strength as Prof. X finally stops him. S.H.I.E.L.D. comes and takes the Juggernaut away. Rogue decides to join the school and is approached by Mystique in disguise. Rogue rejects Mystique who then leaves and reports to a mysterious figure that the Brotherhood has one less member. Senator Kelly is re-elected due to the Juggernaut incident and discusses the Sentinel Program with Trask.