A retelling of Mark Twain’s 1885 novel The Adventures of Huckleberry Finn, James is narrated in the first person by Jim, a young man who is enslaved as a field laborer in Mississippi. We learn from the outset of the novel that Jim uses an affected, uneducated slave dialect whenever speaking to white people, but in reality is intelligent and literate. He lives in a shack on Miss Watson's property with his wife, Sadie, and daughter, Lizzie.
When Sadie overhears that Jim is going to be sold, Jim immediately flees the plantation to avoid being separated from his wife and daughter, promising that he will eventually come back for them. While hiding out on Jackson Island nearby, Jim encounters Huckleberry Finn, a teenager under the guardianship of Miss Watson's sister. The boy says he faked his own death so he could escape his abusive alcoholic father, Pap. Knowing people will assume Jim's disappearance is related to Huck's, Jim takes responsibility for keeping the boy alive on the island.
They survive in a cave and eat catfish caught on a trotline. A house floats by during a flood; inside, Jim finds Pap lying dead, but he won't let Huck see it's his father. When their hiding spot is in danger of being found out, Jim and Huck go down the Mississippi River in a canoe. Along the way, they find books that Jim takes from a group of robbers' bounty. Jim pretends around Huck to be illiterate, and speaks in his feigned slave voice.
When their vessel capsizes, Huck and Jim become separated, with Jim washing up on the Illinois side of the river. Despite it being a free state, Jim encounters a group of slaves who say that their masters pretend they're in Tennessee, owning slaves despite the state law. One of the slaves risks his life to steal a pencil from his master and give it to Jim at Jim's request. Jim leaves his hideout in the woods just as the slave, Young George, is being whipped as punishment for taking the pencil, which he wanted Jim to use to write his story.
Jim reunites with Huck, who had gotten caught up in the dispute between two warring families. They next meet two conmen who pretend to be descended from European royalty. The conmen bring Huck and Jim into a town where a religious revival event is taking place. Their attempt to trick the townsfolk into believing they are missionaries fails, and everyone runs. However, the conmen catch up with Huck and Jim downriver, and discipline Jim into acting as their slave so they can sell him.
While in the possession of a stable owner, having been temporarily loaned out by the conmen, Jim is purchased by Daniel Decateur Emmett, the leader of a minstrel troupe. Emmett, in need of a tenor, puts Jim in blackface to perform with the rest of the group, hoping none of their audience members realize Jim is actually a black man. Jim soon flees the group with Norman, a minstrel performer who is a former slave and who passes as white.
Norman, posing as a slave master, sells Jim back into slavery at a sawmill, the plan being that Jim will escape so they can split the money from his sale. However, their escape is more dangerous than anticipated, and results in the drowning of a female slave Jim tries to rescue. Jim and Norman soon find themselves on an unsafe vessel, so they sneak into the engine room of a riverboat. There they encounter a strange slave who seems never to have left the engine room in which he endlessly shovels coal.
The boat explodes moments later, and Jim bobs in the water, hearing Norman call his name. Huck is also calling for help, having been onboard the boat with the conmen. Jim chooses to rescue Huck over Norman because, he reveals, Huck is his biological son; he and Huck's mother were lovers when young. Huck wants to stick with Jim and live his life as a black man, but Jim insists Huck is better off continuing to pass as white.
Jim and Huck travel several days to return to Miss Watson's plantation. They learn that Sadie and Lizzie have been sold. Jim waits out on Jackson Island again, having sent Huck to find out what he can about who his wife and daughter were sold to. While on the island, Jim takes revenge against the overseer he witnessed raping an enslaved woman by strangling the man and stealing his pistol.
When he learns from Huck that Sadie and Lizzie are in Missouri, Jim sets out to find supplies and more information at Judge Thatcher's home. Jim holds Thatcher at gunpoint and extracts information about the location of the Graham farm in Missouri. He then walks Thatcher to the river and makes Thatcher row him far up the river. After tying Thatcher to a tree, Jim continues on foot until he reaches the Graham plantation, which he learns from a local slave is a slave breeding farm.
At night, Jim frees the male slaves on the breeding plantation from their shackles, recruiting them to seek freedom with him. As a distraction, he sets fire to a field, drawing Graham from his home. Sadie and Lizzie also emerge from their quarters. While one of the male slaves knocks out the overseer, Jim shoots Graham in the chest and flees with his wife and daughter. The novel ends with the trio, alongside the other escapees, arriving in the free state of Iowa. The sheriff asks if any of them is "Nigger Jim." Jim identifies himself as "James," "Just James."
