The movie starts by telling us that in 2011, a lethal virus swept across the planet killing 99% of the population. For the next 400 years, the rest of the population lived within the walled city of Bregna, ruled over by the Goodchild dynasty. We then hear Aeon Flux telling us that in Bregna, everything seems perfect, but beneath its surface, something festers. People disappear never to be seen again with no explanation, and a group of people called the Monicans are the only resistance against the power of the Goodchilds. We then see the best Monican agent, Aeon (Charlize Theron), approaching a man we later learn to be named Claudius. The two kiss passionately, but we then find out that Claudius is really slipping a pill of some sort to Aeon. She swallows and falls into some kind of trance where she meets with the Handler (Frances McDormand), who tells her to place some kind of surveillance egg in the main capital building to spy on the Goodchilds.
That afternoon, we see Aeon walking through some kind of party when she meets with her sister Una (Amelia Warner). She tells Una that she won't be able to make it to dinner that night, and Una, knowing why, says she swishes Aeon didn't do the things she does. Regardless, Una manages to get her sister to come late, and she says that she has a surprise for Aeon, but won't tell her what it is until later. Later, we see Aeon running along a rooftop when she takes out a grapple gun and fires it at the main building. She crosses over and after dispatching security, breaks in. She ignores the requests for identification/authorization, takes the surveillance egg (which looks like the egg in Goblet of Fire), and places it in a pool displaying video images of stuff that has been recorded in Bregna, including the talk Aeon and Una had earlier. She ignores it and goes back up the rope and gets out of there. Meanwhile, we see Una preparing dinner when someone knocks on the door. Thinking it to be her boyfriend Claudius (the guy who pilled Aeon), she opens the door only to get shot by someone. Later, we see Aeon walking up towards Una's apartment complex when she sees Claudius (Nikolai Kinski) coming down. His friends are trying to comfort him ("She was a Monican. You know the law.") but he just gives Aeon a hard glare and says, "She wasn't a Monican." They head down and then a gurney comes down bearing Una's body. As Aeon looks at it, we hear her say in voiceover, "I had a life once...a family. Now all I have is a mission."
We jump ahead one year and see Aeon waking up from some dream filled with blurred figures. She gets up and starts getting dressed when she receives a call from The Handler. Apparently the time is right for the elimination of Trevor Goodchild, who Aeon blames for her sister's death. The Handler gives Aeon the information needed, and Aeon requests that someone named Sitthandra assist her. The Handler agrees to this and the two disconnect. Aeon hitches a ride to the exterior of the capital building and waits for Sitthandra by a wall-window. Sitthandra (Sophie Okonedo) comes and we see that she has two hands where her feet would be, something she suggests that Aeon try. The two get ready and make their way across the complex, dodging organic weapons (vegetables that spit incompacitating darts) all the way. They make it across and split up, agreeing to meet at 1630. Once alone, Aeon reaches into one of her pockets and starts throwing something against the walls of the pipe she's in. Once she's finished, she heads further inside.
Meanwhile, we see Trevor Goodchild (Marton Csokas) and his brother Oren (Jonny Lee Miller) in a meeting with some of the heads of Bregna. Apparently they're a little unhappy with certain policies, and their "leader" is this one big black guy named Giroux (Paterson Joseph). Oren shouts him down and Trevor tells Oren to calm himself. Later, the two brothers are walking and we see Trevor telling Oren that he must remain level-headed, and Oren begrudgingly agrees to do so. Trevor goes to work on a speech of his in some theater. Back with Aeon, she is in the same theatre where Trevor is currently working on his speech. She comes out and holds her gun on him, and he stares at her for a moment and then asks, "Catherine?" Before things can progress, she gets knocked out.
When Aeon wakes up, she finds herself in a small windowless cell. One of the walls disappears and on the other side of some glass, we see Trevor, Oren, and random-Bregnan-security-guard. Trevor sends the other two away and he and Aeon talk, but basically, it comes to "I'm not letting you go, so nyah!" The wall closes up and some water and food comes into the cell. Aeon rolls her head back so that a special eye that can examine stuff comes up and she sees something in the water. She then whistles into the vent above her and the things she was throwing down earlier come running...well, rolling anyway. The marbles form a pyramid outside her cell and blast it open. She leaves, taking the water with her, and on her way out gets a call from Sitthandra. The two talk about how Trevor is still alive, and Aeon gives an order to hold off for a little while. Sitthandra points out that the Handler won't be pleased, but she goes along with it. Meanwhile, we see Oren and some other lady reviewing Aeon's breakout and talking about how she failed to kill Trevor -- which apparently means that he used the Monicans to get rid of his brother so he could assume control. As he and the other lady are talking, Oren freezes the video at one point and looks closely at Aeon's face, apparently recognizing it from somewhere, despite his obvious wishes that he didn't.
Elsewhere, Aeon has caught up with Claudius, who still hates her over the fact that Una got killed when she should have been. Despite this, he still takes time out from his plants to examine the water. He tells Aeon that there's a message inside and the only way to find out what it is, is to drink the water. Reluctantly, Aeon does and gets a message from Trevor saying he wants her to come back and meet with him. He also says that there is a connection between the two of them, and that they knew each other before. She goes to visit him that night and they talk. He keeps peppering her with the big questions (WhyWhoWhat) and eventually the two kiss in a moment of weakness. However, that kiss leads to a longer one with more passion, and the next thing you know...
...we see Aeon waking up in Trevor's bed from another of those wacky dreams. Trevor reaches up to put his hand around her but she whips him around and starts choking him. She lays off in time, gets dressed, and is about to bolt when she notices Trevor's ring lying on the floor. She moves to pick it up and a staircase in the floor opens. Aeon goes down and finds herself in Trevor's private library, which has a dozen or so pictures of his ancestors, all of whom look alike. She touches this one starfish-shaped object, and it comes alive and wraps itself around her. Instead of killing her, though, it takes her to Goodchild's secret lab. She looks around the lab and finds a picture of herself, only in the picture her hair is longer, she's wearing relaxed, more modern (re: our age) clothing, and she seems....happy. She puts the picture down and turns to leave, but immediately encounters Freya (Caroline Chikezie), the Bregnan chief of security. They fight, and Aeon eventually escapes by ducking out the door and letting some needles from Freya's gun penetrate that instead.
Later, we see Trevor being tended to by some medical people while Freya watches. The doctors leave and Freya gives her report. When she gets to the part where she tried to kill Aeon, Trevor freaks, since he wants her alive. Meanwhile, Aeon is sitting outside when Sitthandra climbs up. The two talk and Aeon says that she can't kill Trevor. Sitthandra views this as a betrayal of Monican rules and the two fight, with Aeon eventually winning and tying Sitthandra up and leaving her in a pool somewhere with a breathing straw. While this is going on, we see the Bregnan council watching Trevor have sex with Aeon and deciding that he should be removed and eliminated, which would make Oren the new chairman. Oren's first order of business...find and eliminate Aeon Flux and Trevor Goodchild.
That morning, we see Aeon breaking into some type of balloon that is constantly floating over the city, inside of which are the archives. See, it seems when she was in the lab she got hold of a recorder of some sort and heard her sister's name being said by the people on it. She goes inside and is greeted by the Keeper (Pete Postlethwaite), a 400 year old guy who is apparently alive but only moves about in hologram mode. She goes up to the computer and asks for information on Una Flux. However, she then starts receiving information that she was successfully reassigned as Sasha Pirillo. Realizing what this means, Aeon asks for an address on Sasha, and the next thing we see is Sasha breaking down the door to the Pirillo residence and asking, "Where is she?" The two people at the kitchen table say there's no one there, but then Aeon hears a noise in the back room. She goes to check it out and finds a baby. She holsters her gun and heads over to the baby. She looks at it and sees that it has Una's eyes. Trevor suddenly appears behind her and explains that while the cure his ancestor developed did preserve life for those who took it, it also created sterility, and that every new generation is simply a clone of a clone of a clone, implanted into some other random family at the appropriate time, and then after the gestation period is complete (9 months), out pops baby cloney. However, an issue arose with Una and her test group ((re: the people who get nabbed are part of a "test group") in the search for a cure. While examining her, it was discovered that Una was pregnant -- that nature had made her naturally sterile with no scientific help. Una and her entire test group were killed because of this, but Trevor swears that he had nothing to do with it and doesn't know who gave the order.
While this is happening, we see Sitthandra meeting with the handler and telling her all that has happened so far. The handler realizes that Flux is now a traitor so she calls on three other Monicans around Bregna to get Sitthandra out of her current situation. Once that's done, the four of them will continue Aeon's mission. Meanwhile, we see Aeon giving baby Sasha/Una back to her parents, warning them that she's gonna be a handful. Aeon and Trevor make to leave but an invading Bregnan security force makes them rethink their plans. They eventually escape into a subway, but one of the guards lets loose some fire into their car which injures a bunch of people. Before they can catch their breath, the train is stopped, forcing Aeon and Trevor to break out. Eventually they find a little hidey-hole where Aeon takes a few bullets out of Trevor and puts some skin patches on him to help them heal. He says they need to get to his lab and find the notes for Una's test group, since that would be the set with a cure inside. They head back to the labs and break into a security room at the top of a tower. Trevor does some smooth talking to the green commander of the guards and convinces him to let Trevor and Aeon "borrow" some weapons and armor. The pair take off, and as they're headed for the lab, Aeon asks Trevor who Catherine was. He looks at her and says that she was someone who his previous selves spent their whole lives teaching him about, someone who was taken by the virus before he could do anything about it. She looks at him confused and he says, "You were my wife."
Outside, Sitthandra is patiently waiting in the pool Aeon dumped her in when she is rescued by the other Monicans. She tells them just who the targets are now and starts making plans. Meanwhile, Trevor and Aeon are coming up on his lab/library when he starts to see little pieces of paper flittering down. He runs forward and he sees that his office has been trashed and burned, his notes destroyed, and Freya killed. Disconsolate, he and Aeon head back out, with Aeon trying to say that it's maybe better without a cure, and people are meant to die. Right on cue, more security shows up, this time led by Oren. He tells his brother that he'd rather live forever and subtly admits to what they suspect him of. Meanwhile, Aeon is looking around and notices light glinting off of one of the antennas surrounding them. She realizes Sitthandra is there and attempts to contact her and tell her everything. Sitthandra listens but doesn't decide anything either way. Suddenly Aeon breaks loose and starts going against the guards, and Sitthandra tells her buddies to cover Aeon and Trevor. Trevor tries to make a run for it, but he ends up getting shot (again). Aeon heads for him, dispatching more guards, and eventually after Sitthandra's buddies and most of the guards are dead, Aeon is surrounded in the courtyard by a bunch of guards on the roof. She grabs two machine guns and goes hog-wild with them, taking care of the guards while Sitthandra attempts to take care of Oren. Oren gets a rocket launcher and Sitthandra takes aim, only to hear the click of an empty chamber. Oren fires his rocket and it hits home just before he gets killed by...Trevor! More security shows up and Trevor starts going through the routine of telling them what to do and yadda-yadda-yadda.
Aeon, meanwhile, has one last thing to do. Leaping up to the roof, Aeon grabs hold of the balloon library and climbs up inside it. She starts setting bombs inside when the Keeper shows up. He tells her that 400 years ago, he was told by Oren to destroy her/Catherine after she/Catherine had succumbed to the plague, but for whatever reason, he didn't and he kept her DNA until such time as it was needed. He then nods at the bombs she's placed around the room and tells her, "I'm 400 years old...I'm ready for a rest." She finishes setting the bombs and grabs one of the banners hanging below the library just as they go off. The library slowly starts to descend, with Aeon slipping down the banner a little more every five seconds or so. Finally, just as the thing is about to hit the wall, Aeon drops and hits the ground. The balloon crashes into the wall, utterly destroying it and creating a big hole to the outside world. Trevor comes up and stands beside Aeon while they look at it, and we hear Aeon say, "Now we are free...free to live only once, and die, and make way for the new generation, and let them give us hope that things will be better."
In 2005, we see a woman walking down the street. Behind her, a man -- the original Trevor Goodchild -- comes out of a building and looks around. He sees the woman and yells, "Catherine!" The woman stops and turns around. Trevor asks, "Will I ever see you again?" and Catherine just smiles at him.