John Dillinger (Johnny Depp) is being escorted into prison by a federal marshal. As a group of prisoners work to make clothing, a box is passed around to each prisoner in a suspicious manner. The prisoners all take weapons out of the box and hide them under their clothes. Moments later, an inmate attacks a guard and a break out occurs. Dillinger, who has been recently released on parole, arranged the break out in order to get his mentor, Walter Dietrich, out of prison along with several of his associates. One of the inmates, Charles Makley, loses their cool and shoots a guard, alerting the guards on the outer walls of what is happening outside. The guards begin firing on Dillinger and the escapees. Walter is shot and Dillinger holds his hand as the car drives away, dragging Walter along. Walter slowly dies and Dillinger lets go, allowing the body to slide to a rest on the side of the road. Dillinger then pistol whips Makley and throws him out of the car. They pull over to the side of the road so that Dillinger can look into the horizon and mourn Walter.
Melvin Purvis (Christian Bale) is leading two agents on the hunt for “Pretty Boy Floyd” (Channing Tatum). Purvis chases Floyd through an apple orchard, and a brief gunfight ensues. Purvis calmly aims his rifle from a few yards away and shoots Floyd in the lower back. As Floyd bleeds out, Purvis places him under arrest but watches Floyd die right in front of him. This troubles him a little but he gets over it.
Dillinger and the members of his crew are stationed at a brothel which serves as a safe house, while on their way to Chicago. His men plan a bank robbery and execute it flawlessly. Dillinger pistol whips the bank president and forces him to open the safe. An elderly man pulls his own money out of his wallet, but Dillinger tells him to put it away since he’s only here for the bank’s money. They take a teller, Barbara Patzke (Emilie de Ravin), hostage and take her with them when they drive away. They pull over under a bridge and leave her there with Dillinger’s coat since he doesn’t want her to freeze.
J. Edgar Hoover (Billy Crudup) is before a Senate committee trying to receive a larger budget allocation. The Chairman of the Committee dismisses Hoover as a joke and denies him a larger budget for the fledgling Federal Bureau of Investigation. Hoover makes it clear to his aide that, while denied support in the courtroom, the public will support him through his use of the media. Hoover makes a statement declaring America’s “first war on crime.” He appoints Purvis head of the Chicago task force in order to bring down Public Enemy #1: John Dillinger.
Dillinger is in a restaurant with members of his gang. He sees Billie Frechette (Marion Cotillard) from across the room and is instantly smitten. However, Dillinger’s men insist on talking shop. Homer Van Meter (Stephen Dorff) suggests that the gang start kidnapping people for money since he heard that a recent kidnapping paid off around 100,000 dollars. Dillinger dismisses the idea since kidnapping would make him unpopular with the public. Dillinger reasons that keeping a good light in the public eye protects him from the authorities. Alvin Karpis (Giovanni Ribisi) approaches Dillinger and they talk about a Federal Reserve train loaded with gold which Karpis intends to rob in a few months. Dillinger agrees to think about it since it would leave him set for life.
He sees Billie send a potential suitor away and swoops in to make his move. He introduces himself as “Jack” and asks for a drink. She instead asks for a dance. The pair dance to a song called “Bye Bye Blackbird” and Dillinger takes her out to a fancy restaurant. He tells her that he is John Dillinger and that he robs banks, right from the start. She is shocked by his honesty and tells him that she is just a coat collector at the Steuben Club. She’s starred at by other patrons because she is wearing a three dollar dress, but Dillinger tells her that what matters is not where a person starts, but where they are going. He takes her out so that they can leave when he is stopped by his associates Gilbert Catena and Frank Nitti, two money launderers and bookies. Dillinger tells Billie to wait by the street outside. When he goes outside, she’s gone.
The next evening, Dillinger goes to the Steuben Club and tells Billie that if she’s going to be his girl, she needs to promise that she will never walk out on him again. She retorts that he left her outside and that she’s not his girl. Dillinger tells her he’d never walk out on her and then beats up a rude customer before tossing the man’s coat on him. He tells her she doesn’t need to work here and takes her away. She tells him that she doesn’t know anything about him, and he gives her a crash course on what he likes. She leaves with him and he gives her an expensive overcoat as a present. They make love and afterwards, Billie tells Dillinger about his life.
Purvis lectures the men he has under his command about how he intends to catch John Dillinger. With the coat Dillinger gave Barbara after the robber, Purvis has men check on who sells that type of coat so that they can locate a safe house used by Dillinger and capture him upon a return. They discover that the house used is in fact a gangster car change point. Purvis has men tail the cars coming from the house in the hopes of capturing these “hardened killers.”
Purvis and a group of his men go to an apartment complex they believe Dillinger to be staying at. Purvis visits a room which is paid for under an alias. The door opens to reveal a travelling shoe salesman and his wife eating dinner. Purvis clears the man’s id, but is unsettled by how the man recognized him. He has a guard keep watch and goes to call reinforcements. The man, “Baby Face Nelson” (Stephen Graham) a criminal known for his psychotic ruthlessness -, and his lackey Tommy Carroll kill the agent and escape in a car after a shootout with Purvis and some of his men. Purvis is haunted after watching the agent die, and calls Hoover to ask for Texas Rangers to be sent up to help fight Dillinger, Nelson and the other Public Enemies. Hoover is displeased that Purvis can’t get the job done, but makes the call. Several Texas Rangers are sent up to help the hunt for Dillinger.
An undisclosed amount of time later, Dillinger, Billie, Homer and some other associates are down in Miami watching horse races. Homer makes a joke about how the Midwest is offering a reward for the capture of John Dillinger: Dead or Dead. Billie tells Dillinger that she doesn’t want to be around when he is caught or killed. Dillinger tells her that he’s too smart for that. Catena visits Dillinger and invites him to an exclusive party, to which Dillinger agrees to go.
He and Billie check into a hotel. Dillinger asks about Homer and an associate named Harry Pierpont, who are at the hotel under aliases. The clerk tells Dillinger that he will inform them when they return to the hotel. He goes upstairs and sees Billie naked in the tub. He’s about to join her when Federal Marshalls burst into the room and arrest him. The group were made by the clerk and reported to the authorities. Billie is told to put some clothes on, and Dillinger is dragged to jail.
Purvis visits Dillinger in jail. Dillinger congratulates Purvis on killing Pretty Boy Floyd but notes that Purvis isn’t cut out to murder people or watch them die. Dillinger tells Purvis to get a new job and then tells him he’ll be out soon enough. Purvis tells Dillinger that the only way he will see the outside of a jail cell is when they take him out to execute him. Purvis leaves, visible rattled by the conversation. Dillinger tells the guard he plans to stay in the cell for a little while, but then the guard tells him that he’s going to be extradited to Indiana. Dillinger asks why and tells the guard that there’s absolutely nothing he wants to do in Indiana.
Dillinger is flown to Indiana in shackles and carefully guarded as he is forced from the plane. However, as he is driven to the jail cell, he is greeted with fan fare from the local public. To them, Dillinger is a folk hero. When he arrives in jail, reporters interview him and he poses for a picture with his prosecutor. The media romanticize Dillinger as a jolly man with his court date pending.
At the trial, Dillinger calls a corrupt mob lawyer to serve as his defense. Dillinger faces the electric chair for his crimes and he reasons that he will not be able to escape a federal penitentiary, since most of his friends are inside it already. Knowing that Dillinger could escape his current prison, the mob lawyer tricks its Sheriff, Lillian Holley, into vouching that she has absolute faith that Dillinger could not escape her prison. The judge refuses to transfer Dillinger, so he is allowed to stay in the county jail.
Guarded by a small military platoon along with police officers, Dillinger plans a daring escape. He carves a fake gun out of soap. Dillinger and another inmate called Herbert Youngblood take three guards hostage with the fake gun and then get real guns from the police gun stash. Dillinger and Youngblood take the Warden hostage and take a car along with the jail’s janitor for a ride. They slowly drive buy the military platoon stationed at the front and drive down the street. The stop at a stoplight, right next to a group of soldiers. The soldiers don’t recognize Dillinger, and as soon as the light is green, they drive out of town as fast as possible.
Purvis is ordered by Hoover to use harsher tactics in order to capture Dillinger. With Dillinger on the loose, Hoover stands to lose the little credibility the F.B.I. gained from capturing him. He orders Purvis to arrest his known family and associates on suspicion of harboring, which shocks Purvis. Hoover then goes on to award some young boys in a public ceremony for helping prevent crime in their cities.
Purvis assures his men that they will be able to capture Dillinger since they know what he would come for: Billie. She is being watched 24/7 buy a pair of agents. Dillinger calls her and tells her he’s going to come and take care of her. She tells him not to, but he shrugs it off and tells her he loves her before hanging up.
Dillinger is in need of cash, and tries to get some from one of his safe houses. However, he’s turned away at gunpoint and told to speak with Catena. Dillinger takes Hamilton with him to the club and holds Catena at gunpoint for an explanation. In Dillinger’s absence, Catena and Nitti set up a highly lucrative bookie agency. However, to keep it prosperous, they can’t associate with the Public Enemies. Dillinger is now a persona-non-grata and can’t receive help from any of his old friends. Catena wishes him luck and tells him it wasn’t personal.
Desperate, Dillinger agrees to rob a bank with Baby Face, Hamilton and Carroll. They make plans while at a movie theater, and Dillinger feels unstoppable because of how well he blends into the crowd. They rob the bank, but public opinion has turned against Dillinger during his incarceration. Ordinary citizens, armed with rifles, fire upon the robbers as they leave the bank. Dillinger is shot in the arm and Carroll is shot in the back of the head. Dillinger grabs Nelson by the collar and forces him into the getaway car. The group flees to Wisconsin to escape the heat, leaving Carroll behind to die. Dillinger is stitched up and very displeased that the bank had less money than anticipated. Hamilton wants to quit, but Dillinger tries to convince him to come with him to Reno. Hamilton leaves and Dillinger gets some sleep, intending to leave in the morning.
Purvis and one of his agents arrive at the hospital where Carroll is still alive, but in excruciating pain. The bullet is lodged behind his right eye and the agent presses on Carroll’s eye in order to find the hideout. Purvis is troubled by this, but lets it happen. They get the location and fly out with a group of agents to Wisconsin.
The agents surround the cabin and prepare to launch the assault. Purvis is so obsessed with catching Dillinger that he springs the trap too early when he notices a car driving away from the house. The dragnet isn’t complete, so during the ensuing shoot out, Baby Face is able to escape. Purvis thinks it is Dillinger and orders an agent who acts as his protégé to head Nelson off by car. Dillinger and Hamilton escape into the opposite woods but are pursued by two Rangers. One Ranger shoots Hamilton, but they are able to escape. Baby Face fatally shoots Purvis’s protégé and steals his car. Purvis arrives in time to learn who killed his protégé and has his men pursue the car. He fires his Tommy gun until Baby Face crashes his car. Baby Face tries to shoot his way out, but Purvis brutally puts Baby Face down.
Dillinger tries to drive Hamilton to a hospital, but Hamilton tells him it’s no use. He reminds Dillinger that his biggest fault is his in ability to let go. Dillinger comforts Hamilton until he passes and then drives off to reunite with Billie. Purvis assures his agents that they are close to recovering Dillinger, but he then finds out that Billie escaped her surveying agents and reunited with Dillinger.
On a beach together, Dillinger and Billie hold each other and Dillinger tells her he want to take her to Caracas after helping Karpis on his train robbery. Billie agrees and they spend the whole night together.
That night, Nitti calls Catena and tells him that their entire operation is threatened by a law which Hoover is pushing, which will allow cops to arrest people in any state for interstate crimes. Since their bookie operation is both illegal, and run from coast to coast, Nitti makes it clear that the cops will bust them: unless they provide the Feds with something to prevent the law from passing Dillinger. They know where he intends to take Billie and hole up, and tip the Feds.
When Billie and Dillinger drive to the motel to pick up some supplies, the Feds are waiting. Billie goes in and is captured. She tells them a taxi dropped her off and they arrest her and drag her out. Dillinger sees and grabs a gun and starts walking toward her, but she is driven away in a squad car. Dillinger returns to his car and drives away, crying for his lost love.
Billie is brutally beaten by an interrogator referred to only as “Fatboy.” She tells Fatboy that he is an idiot for believing that she was dropped off in a taxi and that if he had only turned his head, he’d have seen Dillinger. She tells him that if Dillinger finds out what he did, Dillinger will kill him. He beats her with a phone book, but the women in the F.B.I. are disgusted and Purvis and Agent Sopsic intervene on her behalf. Purvis tells her where the ladies room is, but Billie can’t walk. Purvis carries her there and the office women help her out. She is sentenced to two years in prison for aiding and abetting. She sends him a note via his lawyer telling him not to break her out and that two years is nothing.
Dillinger moves on with his life. He visits an old woman, Anna Sage, whom he had a fling with and begins dating her daughter, Polly Hamilton (Leelee Sobieski). Polly wants to go get her waitressing license and Dillinger offers to drive her and help with her other chores. Meanwhile, Sage, hoping to avoid deportation to Romania, agrees to help Purvis capture Dillinger. She tells him that they will be going to a movie tonight at one of two theaters. Agent Sopsic tells Purvis that Dillinger sure as hell wouldn’t see a Shirley Temple film and the group identify the theater. Purvis takes his men to the theater to begin recon, leaving a few behind.
Dillinger goes into the police station with Polly and walks into the Dillinger Task Force room. He looks at all the photos of himself and his dead friends. He smiles when he sees its agents huddled around a radio listening to a baseball game. He asks them the score, and though the look at him, they don’t recognize him. He smiles as he walks out.
That night, Sage wears clothes designed to signal Purvis and his men (an orange dress with a white shawl). Sage, Polly and Dillinger catch a showing of Manhattan Melodrama, starring Clark Gable, at the Biograph Theater. After the showing, the agents pursue Dillinger as he walks down the street. Fatboy in the lead, he cocks his gun and prepares to shoot Dillinger but Dillinger turns around and intimidates him, preventing the shot. Agent Purvis runs toward Dillinger, but Agent Sopsic shoots Dillinger through the head when he sees Dillinger reach in his pocket…for a pocket watch with Billie’s photo in it. As Dillinger lies dying, he whispers his final words to Sopsic. Purvis asks what they were, but Sopsic says he couldn’t hear. Purvis walks away, more disgusted than proud. Reporters and a crowd gather over Dillinger’s body.
A few days later, Sopsic visits Billie in prison. She heard about Dillinger’s death and knows Sopsic killed him. He tells her that before he died, Dillinger said “Tell…Billie…Bye, Bye…Blackbird.” He leaves and Billie starts crying as the door closes.
The epilogue reveals that Billie moved back to Wisconsin after her release, until the day she died. Purvis quit the F.B.I a year after Dillinger died and took his own life in 1960.
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