An unnamed man (referred to in the credits as "Buscemi") (Steve Buscemi) walks into a bar. The customers are initially hostile towards him but he seems not to notice. He begins to tell how he was in a bar in another town and it was cleaned out by a man in black looking for a man named Bucho. This story openly frightens the men and the bartender (Cheech Marin) and his side kick Tavo (Tito Larriva), attempt to get a description of the man's face. Buscemi claims to not know and remarks that he believes the man is headed that way. El Mariachi (Antonio Banderas), the man from the story wakes from a dream about Domino, his love interest in the first film. He hears a knock at the door and lets in Buscemi. It is revealed that Buscemi is helping El find out where Bucho is. He tells El that he can find out where Bucho is at the bar he just visited. Buscemi asks El what he will do when he has his revenge. El simply states that it will be over. Buscemi then says he is glad. El remarks that Buscemi never had the stomach for that sort of thing. He replies: "Neither did you." El then cleans himself up to appear as a mariachi and walks to town. He meets a young boy and teaches him to loosen his fingers when playing the guitar, despite not being able to use his fingers on his left hand due to the gunshot wound to his hand from Moco in the first film. Meanwhile, Bucho is apparently worried that "the man in black" is coming for him. He orders his men to keep an eye out for any strangers and buys a bulletproof limo. El then goes to the bar. The patrons are suspicious of him due to the Buscemi's story even though he appears nothing like he was described ("The biggest Mexican ever!") except for the black clothing. They hold him at gunpoint as they open his guitar to search for weapons that they were told were in the guitar case ("The biggest hand cannon I've ever fucking seen!"), but only see a guitar. They let him go, just as the guitar is revealed to be a cover inside the case to conceal his guns. They prepare to kill him but he ejects 2 hidden Ruger P-380 .45 ACP pistols from his sleeves and engages in a bloody gunfight with the men. Meanwhile in a hidden room, several other men see the gunfight on a video monitor and Tavo executes the drug Pick-Up Guy (Quentin Tarantino) because they believe he betrayed them. El proceeds to kill all the men except the bartender and tries to question him, as he was trying to force him to take El to Bucho but he is accidentally shot in forehead by a man from the hidden room. They attempt to shoot each other but run out of bullets and try to use the fallen men's guns but find that they are all empty. Finally the man finds one and tries to shoot El with it, but El snaps his neck. He then leaves the bar, unaware that he is being followed by the bartender's friend and associate of Bucho, Tavo, who is carrying two pistols a Desert Eagle and a Ruger P-380 in public. As he walks, he notices a beautiful woman (Salma Hayek) walking towards him. Her shocked expression at the man behind him warns El and he shoves her out of the way in time as he is shot in the arm, but manages to kill Tavo. The woman then carries him away. El awakens in a bookstore to see the woman stitching up his arm. She says her name is Carolina. He wants to go to a hospital but she says he wouldn't if he saw them. He then asks where he is and she says it is her bookstore, but business is not very good. He then falls asleep from the painkillers she gives him. Carolina runs some errands and then comes back to the bookstore. Curious about his guitar case, she opens it to see the guitar, but it then opens to show his guns. She is then grabbed by El. She says she now knows who he is ("You're that guy you always hear stories about.") She doesn't seem to be afraid of him. He then offers to give her one of his guns as a gift, but she declines. He then leaves to go to church, where he meets with Buscemi who tells him to get out while he still can, because that is what he is doing. El then follows and begins to argue with Buscemi, again unaware that he is being followed, this time by another man in black (referred to in credits as "Navajas") (Danny Trejo), who has been stalking El throughout the film. He then tells Buscemi that maybe he should quit after all. Buscemi approves of this, but is then killed by Navajas' throwing knives. El is then also hit, but only wounded and takes cover in an alley. Navajas waits confidently at the entrance. Bucho's limo, full of armed men and Bucho's girlfriend, pulls up behind him and attempts to question him on who he is. He proceeds to kill several of them with his knives, but is then shot dead. El manages to escape without being seen and runs into the little boy from earlier, who wants to show El his real guitar. El follows him, visibly in pain and bleeding profusely. A car drives up and a man inside trades guitars with the boy. They then drive around the corner and see El. The man in the car attempts to pull a gun, but El is faster and demands the other guitar. They give it to him and drive away. He then breaks it open to see a packet of cocaine. He then questions the little boy who says that everyone else in the town is involved and most of the businesses are fronts, including Carolina's bookstore. Enraged, El heads back to the bookstore. Meanwhile, Bucho's men return Navajas' body. He calls his superiors to ask for a description of the man they sent in to look for El. The description matches Navajas, but Bucho doesn't let on that his men killed the man they sent. He then chastises his second in command for believing that El is nothing but a legend. El, returning to the bookstore, yells at Carolina, angered at the fact that she is apparently working for the man who he is trying to kill, and that his friend is dead. She then states that she doesn't work for Bucho, stuff is only dropped off and picked up from her bookstore and she is paid 50,000 dollars a year. She says she uses a little to keep the bookstore running and saves the rest in case she ever has to leave, but that once she joined she wasn't allowed to get out. El calms down and lays on the counter so she can fix his wounds, but she promptly shoves him off behind the counter just as Bucho walks in. He questions her about if she has seen any strange people, but she states that she hasn't and will call him if she does. El, behind the counter attempts to load his gun silently, but is unable to in time before Bucho leaves. He attempts to leave and follow Bucho, but Carolina tells him that it would be suicide and to wait till later. Later, while El is recovering from his wounds, Carolina gives him a guitar as a present. They attempt to play together, but are unable to. Carolina then kisses El, and they proceed to have sex in her bedroom. Meanwhile, Bucho calls his men in town and tells them to search the bookstore and if El is there, to kill him and Carolina by burning the bookstore down. The next day, El awakens while Carolina sings with her eyes closed, to see the silouhettes of armed men through the curtains. He proceeds to silently pull out one of his pistols and his sawed-off double barrel shotgun and trips Carolina out of the way as he fires and kills the two men. They attempt to escape through the bookstore, only to see that it's on fire. They make their way to the roof, gunning down several men, only to find their way blocked by men on the ground. Carolina jumps while El fires at the men and then throws his guitar case across to the next building. Men then come behind him and he is forced to jump backwards off the roof while firing at the crooks. He lands, and rolls, unharmed. He then uses a grenade to kill the last of the gangsters. While hiding on the roof, El sees Bucho drive up. He proceeds to aim a scoped Wildey Magnum pistol at Bucho's head but hesitates when he sees Bucho's face, and puts the gun away. Carolina asks him why he didn't shoot him. El doesn't answer, and they take refuge in a hotel. El tells her that she can escape and use the money she stashed to start a new life, without El having to kill Bucho, but Carolina says that the money was hidden in the books that were burned. El then decides to call his friends Campa and Quino. They show up shortly after and follow him to a deserted part of town, where Bucho's men find them. Campa and Quino reveal that they have special cases, too, Campa's two cases being machine guns, and Quino's case being a rocket launcher. They proceed to kill many of Bucho's men along with Carolina's help. However, Quino is killed by a gangster on a roof, and Campa is killed when he runs out of ammo. The little boy is also caught in the crossfire and is badly wounded. El and Carolina kill the last man, Bucho's second in command, by running him over, and rush the boy to the hospital. With the doctors unsure if the boy will live, El angrily heads to Bucho's ranch to settle the conflict. They arrive and find themselves surrounded, but Bucho calls his men off. It is then revealed that El and Bucho are brothers; this being why El did not kill Bucho earlier. Bucho, however, angry at Carolina's betrayal, tells El to put his hands up while he kills Carolina and that they will then be even for El killing his men. El, unable to bear another love's death, ejects his pistols from his sleeves as he did earlier in the bar, and shoots Bucho dead. El and Carolina are later seen at the hospital there they get to know the boy has survived and is getting better. El tells Carolina he will thank her and leaves.Then walking in the desert Carolina drives by him with a jeep and asks him to join her. El throws away his guitar case and he and Carolina drives and stops and goes back for the guitar then drives away in the sunset.