Two hitmen, Tommy (Michael Stuhlbarg) and Larry (Michael Pitt), are having a discussion about shooting people in the eyes, considering they are sent to kill their employer's girlfriend. With their backs turned, they don't see a figure in a red ski mask come from behind them and shoot them both in the head. The figure throws two Jack of Diamonds cards on their corpses. A title card appears and reads "PSYCHOPATH NO. 1".
We meet Marty (Colin Farrell) waking up to hear a message asking when he'll be done with his next screenplay. Downstairs, his girlfriend Kaya (Abbie Cornish) is doing yoga until Marty's friend Billy (Sam Rockwell) comes in. After she leaves, the two of them go watch a movie, and Marty asks Billy how the "dog kidnapping business" is going, but Billy prefers to think of it as "dog-borrowing".
We see a scenario in which Billy and his partner Hans (Christopher Walken) are looking for a dog to swipe. They take a basset hound from a young blond woman, and as soon as she puts up posters searching for her dog, Hans goes to her house, returns the dog, and collects reward money. We see that Hans is using this money to help his ailing wife Myra with her cancer treatment. She is aware of his business and wants him to take an honest job, preferably in government (Hans points out the irony).
Marty and Billy are out drinking while Marty complains about not being able to finish his script, titled "Seven Psychopaths". Billy gets out an article he read in a newspaper of the "Jack o' Diamonds Killer" who kills high-ranking members of the mafia. Marty likes the idea and writes it down. Billy asks to help with writing the film, but Marty doesn't respond.
At home, Marty is trying to come up with his second psychopath after the Jack o' Diamonds Killer. He comes up with a story that we see of a Quaker man whose daughter is killed. The killer feels guilty and turns himself in. He asks for execution but is given a 27-year sentence. In prison, the killer becomes religious, and through time, he proves he is a changed man and is released early. However, he becomes haunted by the presence of the Quaker man. Eventually, he goes mad and decides to end his life, because he knows there is a place in Hell for him if he commits suicide. He slits his throat as he watches the Quaker standing outside his window, but the Quaker takes out a razor of his own and slits his own throat so the killer can see. Title card reads "PSYCHOPATH NO. 2".
Kaya throws a party sometime later, and Marty is retelling his story to an amused crowd. Billy says he helped write it, but Marty, very drunk, rudely tells him off.
Marty wakes up on Billy's couch with a Shih Tzu on him. Billy tells Marty that Kaya threw him out because he called her a fucking bitch. He calls her to confirm the truth.
We meet Charlie Costello (Woody Harrelson) aka "PSYCHOPATH NO. 3" interrogating Sharice (Gabourey Sidibe) over the disappearance of his dog Bonny (the same dog in Billy's place). She is scared shitless, trying to tell him that the dog was just taken when her back was turned. One of Charlie's guys, Dennis, tells him that there were a noted number of dog kidnappings in the area, and Charlie orders his guys to get the dog back, and he lets Sharice go.
We cut to a motel room where a Vietnamese priest (PSYCHOPATH NO. 4) is sitting on a bed as a hooker enters the room (semi-important later). He mentions wanting to kill all American citizens over their involvement in the Vietnam War.
In thee dog warehouse where Billy and Hans keep their dogs, Marty discovers an ad Billy took out in the newspaper asking other self-proclaimed psychopaths to call and help Marty find inspiration. He is NOT happy about this.
Dennis and Al (another goon of Charlie's) stalk Hans and capture him, having him lead them to the warehouse to find Bonny. They barge in and aim a gun at a frightened Marty, but soon after, the Jack o' Diamonds killer enters and shoots Dennis and Al, then drops the playing cards on their bodies and leaves.
Marty and Hans go into Billy's home as Marty is covered in blood and puke. Hans informs Billy of the situation, and they determine that their kidnapped dog belongs to a dangerous man (it also helps that Bonny's dog tag reads "If lost, return to Charlie Costello or you will fucking die"). They go to a bar and try to figure out what to do.
Marty and Billy go back to Billy's place and find an old man with a rabbit waiting outside for them. His name is Zachariah Rigby (Tom Waits), and he wants to tell his story. Marty gets him some tea as he recounts his tale - he and a black woman, Maggie, started a romance in their youth as they went around the country killing off other serial killers. They get a man who stalks them in their car by dousing him with acid, lighting him on fire, and shooting him. They also behead a man in an asylum. When they arrive to them home of a hippie (noted as being the Zodiac Killer), Zachariah failed to assist her in the killing because he was more preoccupied with a rabbit that is almost splashed with gasoline as Maggie is about to light the hippie on fire. As he burns to a crisp in his home, Maggie breaks it off with Zachariah, leaving him heartbroken. After he finishes his story, he asks Marty to include a message to Maggie during the credits of his film, letting her know he still loves her. Marty agrees. As Zachariah leaves, Marty lists him and Maggie as Psychopaths No. 5 and 6.
Charlie goes to look for Hans's wife at the hospital, not knowing she is black and assuming she is not in the room when he finds Myra. He asks when she will return so he can find out where Hans is. He eventually realizes she is his wife and then shoots her as she says her last goodbye. As he leaves her room, he passes Hans coming with a bouquet of flowers, where he overhears Charlie talking about wanting to hear the woman's husband scream. Hans does find Myra's body and cradles her for a while. He goes to the waiting room to find Charlie, who asks him about what he is wearing around his neck (a cravat). Hans offers to give it to him, even taking it off to reveal a large slit scar in his throat. Repulsed, Charlie leaves.
Billy is making out with his girlfriend Angela (Olga Kurylenko). She is also Charlie's girlfriend, so she understandably freaks out when Billy brags about kidnapping his dog. She gets a call from Charlie as Billy gets a call from Hans, who tells him in front of Marty that he knows Charlie killed Myra. After he hangs up, he shoots Angela in the stomach, then hands her a Jack of Diamonds card, revealing that he is the masked killer. Title card reads "PSYCHOPATH NO. 7...AND 1".
Marty comes across Billy's diary, revealing more about himself. He wishes he were a better person to people, particularly Kaya and Marty, but especially to Marty, calling him "the best writer of his generation". Billy comes by to get Marty, Hans, and Bonny. They drive off to get away from the villains. Charlie, meanwhile, cries over Bonny while his other goon Paulo tries to calm him down.
In the car, Marty sincerely asks Billy for help with writing his script, which Billy happily accepts. They go to a bar where Marty tells Hans about the Quaker story. Hans realizes where this is going, and he reveals his throat scar to Marty and Billy. Back in the car, Hans informs Marty that his story isn't totally accurate - he is indeed the Quaker from Marty's story, and his daughter was black. Hans, after surviving the ordeal, tried to find peace through the words of Gandhi. Marty says he wants his screenplay to focus on themes like the "eye for an eye leaving the whole world blind". He wants his film to be about peace and love, and not just violence and carnage. Billy disagrees and thinks that it SHOULD be violent, considering the film is about, well, seven psychopaths!
The trio and the dog stop off in the desert during the day. Hans is reading Marty's script and gives certain critiques, like the uselessness of the female characters, but he is most intrigued by the Vietnamese priest. Marty says he doesn't even know what to do with that, but he just liked the idea of a Vietnamese man in a priest's outfit. He imagines a scenario in which he comes home to his village from battle to his wife and daughters, but they are all dead. He would've gone out to kill the people responsible, and then have the aforementioned hooker go to a convention with a bomb strapped to her.
At night, Billy comes in with an idea for the movie featuring an incredibly over the top climax with a shoot out. In it, which we see, the Jack o' Diamonds Killer is waiting with Bonny in the cemetery as the boss (Charlie) comes in with all his men, armed to the teeth, and begin an epic shoot out. The killer starts shooting while Marty is writing what he observes. Meanwhile, the other psychopaths (Hans, Zachariah, Maggie) enter the shoot out. Even the Vietnamese guy comes in with a flamethrower. Somehow, Kaya comes in as it starts pouring rain (a great little wet t-shirt moment) and is calling out for Marty, but she gets shot to Hell as Marty cries out. He joins in this shoot out as the villains kill Zach, Maggie, the Vietnamese guy, and the Diamonds Killer. However, as Charlie is about to kill Hans and Marty, the killer somehow pulls out a crossbow and shoots Charlie in the neck, and then pulls out a shotgun and blasts Charlie's head clean off. Marty and Hans go to the killer and have a tearful moment with him ad the imaginary camera pans out to the moonlight with Billy's message of peace and the like. A perplexed Marty and Hans look at him and say its interesting.
The next morning, Marty and Hans go to a shop and find a newspaper with Billy and Angela on the front page. He is suspected of the "Jack o' Diamonds" murders, and Marty and Hans piece it together. They go back to their campsite to try and talk to him, but they spend the rest of the day drinking and having a peyote party. During their little trip, Marty asks Billy why he killed those people, and Billy says he thought it would help with the movie. Marty says he doesn't want to work with a killer, which cuts Billy. Marty goes to find Hans, who thinks he just spoke to Myra, sitting on a chair in a room, but Marty says its just the peyote (later revealed to be Billy making voices) Suddenly, their car explodes, and they run to see if Billy's okay. He was hiding in the tent with Bonny, and he tells the guys he called Charlie to come find them by himself and to look for the burning car.
In the morning, they wait for Charlie to come around. Hans has gone off walking somewhere, leaving Marty and Billy with Bonny. When Charlie does come around, Billy checks to see if he is armed, and although he's not, Billy shoots him in the back anyway. He still thinks he's got a gun and checks his car, but all he finds is a flare gun. Charlie asks for his dog back, but Billy refuses to give it to him.
In the welcome center closer to town, Hans walks near Paulo and other goons. Paulo threatens him with a gun, but Hans doesn't even flinch. They stand there awkwardly avoiding the police.
Marty pulls Charlie into the car to take him to the hospital, which Billy finds unbelievable. He fires the flare gun, which Paulo sees. He gets the other guys to go. Hans calls after them and begins to pull something out of his jacket, so they shoot him down. The cops see and try to shoot after the goons, but they get away. The cops go to a dying Hans, who is holding a tape recorder.
As Marty is driving Charlie away, the other guys stop before them, and Charlie gets out. Paulo mentions killing Hans, which upsets Marty. Charlie almost decides to kill Marty, but when he doesn't show fear, he has him move aside so they can go back to get Bonny. They all go back to where Billy and Bonny are, which is the "perfect place for a shoot out". Billy fires and kills all of Charlie's guys except Paulo. They have a standoff, where Billy threatens to shoot Bonny Si the flare gun, or Charlie will kill Marty. They eventually decide to let Marty go off after they conclude that he had nothing to do with this. He drives off. Charlie tries to shoot Billy, even though his gun is constantly jamming. He finally gets to shoot Billy in the head right as the cops are coming. Charlie calls for Bonny, who doesn't come to him. The dog stands next to a dying Billy, who asks for his paw (a running gag in the film). Bonny gives him a paw, and Billy smiles as he dies. The cops arrest Charlie and Paulo.
Marty finds a crowd standing over Hans's corpse. He is allowed to take his tape recorder. He listens to it and hears a message Hans left regarding an idea for the Vietnamese psychopath. The man still meets with the hooker, dressed in a red dress (as opposed to just being imagined in her panties as earlier). They start to make love, but he hears "Desist, brother" in his language. He takes the woman to the convention with the bomb strapped to her and then pours gasoline near her. She, having learned Vietnamese, tells him "Desist, brother, this will help us". He closes his eyes and then is sitting in a crowd on a street in Saigon, dressed like a Buddhist monk. He's drenched in gasoline, as another monk repeats the phrase that the hooker said. The priest says it will help him. He commits self-immolation as the hooker watches in tears. Hans concludes that this psychopath decided not to choose a dark path as the others did.
Sometime later, Marty finishes the script and has it all typed up and ready to go. We see that he is now taking care of Bonny. He leaves his home and starts walking down the street.
The credits start to roll, until we see Marty getting a call from Zachariah. Apparently, Zachariah saw Marty's film and noticed his message to Maggie was not included. Marty apologizes but Zach says he will be coming on Tuesday to kill him. Marty responds quietly and somewhat indifferently. Zach notices he sounds a bit different. He then says they will set this up some other time. He hangs up and leaves with his rabbit.
You can send in your spoiler to other movies by going here.