"Tom" finds an old man in his room in St. Louis when he returns one night. To his surprise, the old man turns out to be Roxy, who is in disguise. He stammers out an apology for selling her "down the river" and she begins to cry, telling him that he has treated her worse than anyone would treat a dog. She tells him that she was treated well at first, until the plantation owner's wife became jealous of her. Then she was sent out to work in the fields and abused horribly at the wife's insistence. Finally, after seeing the overseer beat an orphan girl who had tried to sneak Roxy some food, Roxy attacked the overseer and stole his horse. She made her way to the river, and eventually on board a steamboat, the Grand Mogul, on which she had once worked. The crew, old friends of hers, found her new clothes and gave her some money. She has been waiting in St. Louis for "Tom." Not long after her arrival in St. Louis, though, she saw her new master, posting runaway slave bills offering a reward for her return. "Tom" is frantic. Roxy's master has written him, saying that he suspects that something was not right about the sale and letting "Tom" know that he has heard that Roxy is in St. Louis. The man threatens "Tom" in the letter, telling him that he had better return Roxy to him or there will be trouble. "Tom" cannot believe Roxy would jeopardize him by coming to see him.
As it turns out, "Tom" has actually set a trap for Roxy, knowing she would come. Roxy outsmarts him, though, telling him that he must buy her back in her own name by giving her master all the money he has and begging the rest from Judge Driscoll; otherwise she will reveal his true identity and have him sold "down the river." After demanding that her new bill of sale be sent to Pudd'nhead Wilson, Roxy forces "Tom" to escort her back to her hiding place. She shows him a knife and tells him that she will kill herself if she's caught and that she will kill him if he signals to anyone. After dropping Roxy off, "Tom" walks home dejected. He decides, though, that he will rob his uncle rather than ask him for money.
Luigi issues a challenge to Judge Driscoll, who refuses it, saying that it would damage his honor to duel with an assassin. Pudd'nhead tries to convince the judge that Luigi killed only out of self-defense, and that to duel with him would be no shame, but the judge stands firm. Pudd'nhead tells Luigi that the "law" of the region requires him now to try to kill the judge on sight, and for the judge to try to kill him; he warns Luigi to be careful. That night the twins go out for a walk.
"Tom" returns to Dawson's Landing that night as well. He enters the judge's house and finds him asleep in his study with his money spread before him. Grasping the twins' Indian knife, "Tom" moves toward the money. He accidentally drops the knife sheath and the judge wakes. He seizes "Tom" and cries for help. "Tom" stabs the judge, who falls dead. He throws the knife down and rushes to his room upstairs. Quickly he changes into girls' clothes. The twins, who have been out walking, burst into the house and find the judge dead. Other neighbors arrive and "Tom" sneaks out the back way, encountering a few neighbor ladies, who do not recognize him in his disguise. He returns to St. Louis, and the next morning sees a notice in the paper about the judge's death which also informs him that one of the twins has been blamed (the motive is given as the election) and will probably be lynched. "Tom," now the heir to his uncle's money, pays off Roxy's master and mails the bill of sale to Pudd'nhead, as Roxy has requested. He is thankful that Pudd'nhead had made it impossible for him to sell the knife, which has been the instrument of his freedom. "Tom" heads back to Dawson's Landing, feigning shock at the judge's death.
Pudd'nhead takes charge of the murder scene, securing it for the constable. He also detains the twins, although they assure him that they found the judge dead. They also point out that they have no blood on them. Pudd'nhead tells them he will do what he can for them. He has noticed some fingerprints on the knife. The coroner's jury indicts the twins, who are put in prison. Pudd'nhead remembers the woman who has been blamed for the earlier robberies, and wonders if she might be responsible. The bloody fingerprints on the knife are not either of the twins', so Pudd'nhead compares them to all the female prints he has in his files; none match. Pudd'nhead does not believe the twins are guilty, but he also refuses to suspect "Tom," since he believes that "Tom" did not know that the judge's will had been renewed. He also believes that "Tom" was in St. Louis when the murder was committed. Pudd'nhead knows he must find the killer by matching the fingerprints on the knife; the twins will be executed if he does not. "Tom" pretends to be grief-stricken, although in reality he is haunted by his last glimpse of the dead man. Everyone believes his emotion to be genuine.
Roxy's escape and the judge's murder give Twain a chance to indulge in some melodrama. While these are some of the most serious moments of the book, they draw on sensational popular fiction too. Roxy's experience on the plantation lets Twain hint at the controversial issue of miscegenation--the planter seems to be sexually attracted to her--but it also gives him a chance to expose the immediate physical horrors of slavery without jeopardizing the rest of his story. By making those "down the river" the ones responsible for the truly bad stuff, Twain allows the people of Dawson's Landing to appear more ambiguous in their treatment of blacks, even though those blacks are still being held as slaves. Roxy's escape and her subsequent fear of the slave-catcher also lend some legitimacy to some of her own questionable doings: we see for the first time the real threat she faces.