Johnny (Joseph Gordon Levitt), a cocky young gambler, arrives in Sin City and heads to Kadie's place, where he immiedetly hits the jackpot on multiple slot machines. Taking a young waitress, Marcie (Julia Garner) with him as a good luck charm, he buys into the backroom poker game lead by the all-powerful Senator Roarke (Powers Booth). Johnny repeatedly wins in the high-stakes game, and cleans the senator out. One of the other players, the corrupt police lieutenant Liebowitz (Jude Ciccolella) warns him to get out of town, but instead Johnny takes Marcie out for a night on the town. He is walking her home when he is attacked by Roarke's goons. He fights them off and tells Marcie to meet him at a hotel before he is escorted into a waiting car. The Senator is waiting for him. In payment for the humilation he suffered at the card game, Roarke takes back his money, then reveals a pair of pliers, which he uses to break three of Johnny's fingers. They toss him from the car and the Senator shoots him in the leg, at which point he reveals that he has recognized Johnny as his illegitimate son, but remarks that he only considered his dead son Roarke Jr. (who was killed during the events of the first film) his flesh and blood. He leaves Johnny alive, preferring to let him suffer, and Johnny swears revenge.
Johnny visits an unliescened doctor, Kroenig (Christopher Lloyd) who shoots up heroin before trading his services for Johnny's last forty dollars and his shoes. Realizing that he has left Marcie unprotected, Johnny flees to her hotel, but finds the Senator waiting for him along with Marcie's dismembered head and hands. Again, the senator lets him go. Intent on taking down Roarke, Johnny is able to scrounge a dollar from a sympathetic waitress (Lady Gaga) which he uses to regain enough money playing slots to buy his way into Roarke's game the following night. Playing with significantly less confidence, Johnny folds his first few hands, allowing Roarke, who taunts him about his dead mother. He is able to once again con Roarke into going all in, and then reveals his winning hand. Johnny taunts his father, reminding him that the story of how he was beaten twice by the same man will follow him for the rest of his life. His vengeance completed, Johnny smiles resignedly as Roarke shoots him in the head, commanding his men to get rid of the body.