The novel begins with Huck himself writing the story. He briefly describes what has happened to him since "The Adventures of Tom Sawyer." Huck was adopted by the Widow Douglas and Miss Watson, both of whom took pains to raise him properly. Dissatisfied with his new life, Huck runs away. Tom Sawyer manages to bring Huck back by promising to start a band of robbers. However, many of them soon become bored with the make-believe battles and so the band falls apart. Pa returns to find Huck and his money.

Judge Thatcher and the Widow try to gain court custody of Huck, but a new judge in town refuses to separate Huck from Pa. Huck soon decides to escape after Pa starts to frequently beat him. After running away Huck runs into his old friend Jim, who was Miss Walton's slave, before he decided to run away. Jim is frightened at first, believing Huck to be dead, but soon is happy to have a companion. The river starts rising, and at one point an entire house floats past the island. Huck and Jim climb aboard to see what they can salvage.

They find a dead man lying in the corner of the house, and Jim goes over to look. Jim realizes that the dead man is Pa, and he carefully refuses to tell Huck who it is. Using a large raft, they float downstream during the nights and hide during the days. Jim and Huck continue floating downstream, becoming close friends in the process.

Huck rescues two con-men named Huck and "the King." Farther down the river the King and Duke sell Jim into slavery. Huck decides to rescue Jim, and daringly walks up to the house where Jim is being kept. Luckily, the house is owned by none other than Tom Sawyer's Aunt Sally. Huck immediately pretends to be Tom.

When Tom arrives, he pretends to be his younger brother Sid Sawyer. Together he and Huck contrive how to hel Jim escape from his "prison," an outdoor shed. That night they get Jim and start to run away. The local farmers follow them.

Huck, Jim, and Tom manage to escape, but Tom gets shot in the leg by a farmer. At this point Aunt Polly appears, having traveled all the way down the river. She realized there was something wrong when her sister wrote her that both Tom and Sid had arrived. Aunt Polly tells them that Jim is indeed a free man, because the Widow passed away and freed him in her will.

Jim then tells Huck to stop worrying about his Pa. He reveals to Huck that the dead man on the floating house was in fact Huck's Pa. Huck then concludes the novel by stating that he would never have undertaken the book had he known it would take so long to write it.