At Georgia Pines retirement home, an elderly Paul Edgecombe sets to write about the events of his time as a correctional officer at Louisiana’s Cold Mountain State Penitentiary with the help of his companion, Elaine Connelly. In 1932, a 40-year old Paul is the supervising officer of Cold Mountain’s death row, formally referred to as E Block, but known commonly as The Green Mile, for the color of its linoleum floor. This is the same year that John Coffey, a large black man found guilty of murdering the Detterick family’s twin girls, arrives at Cold Mountain. He was found clutching the white girls’ dead bodies and despairing over their deaths. Paul is unsettled by his gentle demeanor. One day, Coffey beckons him to his cell and cures Paul of his urinary tract infection. Paul struggles to reconcile Coffey’s healing powers with the horrific nature of his crimes. Later, Coffey uses his healing powers again to revive Mr. Jingles, the pet mouse of another inmate, Eduard Delacroix, after the guard, Percy Wetmore stomps on it. The rest of the guards, Brutus “Brutal” Howell, Harry Terwilliger, and Dean Stanton witness the revival, and come to believe in Coffey’s magical abilities.

Meanwhile, William Wharton joins The Green Mile as an inmate after a wild crime spree. A reckless and violent man, he attempts to choke Dean Stanton to death at first meeting. One day, Wharton grabs guard Percy Wetmore from his cell and scares the guard into wetting his pants. Delacroix makes the mistake of laughing at Percy. Furious and embarrassed, Percy vows to take revenge on Delacroix on the day of his execution. When Delacroix sits at Old Sparky, the electrocution chair, Percy intentionally omits the brine on the sponge of Delacroix’s helmet. As a result, he prolongs the pain of Delacroix’s death and his body burns over the course of his excruciating execution. The rest of the guards are furious with Percy as they have grown fond of Delacroix and believe he did not deserve such a horrific death.

Paul decides he must atone for his complicity in Delacroix’s painful death by helping Warden Hal Moores’ wife, Melinda, with her brain tumor. He enlists the help of guards Brutal, Dean, and Harry to break Coffey out of prison temporarily, so he can cure Melinda with his healing touch. As part of their plan, they give inmate Wharton a sedative and trap Percy Wetmore in the restraint room. Before they leave, Wharton appears to still be conscious in his cell and reaches out to grab Coffey’s arm. At that moment, Coffey realizes that Wharton is the real killer of the Detterick twins, although that fact is not known to the others at the time. At the Moores’ house, Coffey removes Melinda’s brain tumor by sucking it out of her mouth through a deep kiss. Melinda wakes up in full health and expresses her gratitude to Coffey. The guards make their way back to Cold Mountain with Coffey successfully. Upon releasing Percy from the restraint room, they make him promise to send in his transfer to Briar Ridge, another penal institution. A bitter Percy walks free, but not before Coffey grabs him and releases the forces of Melinda’s tumor into his mouth. When Coffey releases him, Percy stumbles towards Wharton’s cell and shoots Wharton six times, killing him while Wharton is sedated. The guards apprehend Percy, who is transferred to Briar Ridge as a patient, instead of a guard, and remains in his catatonic state from Coffey’s touch.

Later, Paul investigates the murder of the Detterick girls and learns that the true killer is Wharton. Around the time of the murder, Klaus Detterick, the girls’ father, had hired Wharton to help paint the barn, unaware of his criminal background. Wharton kidnaps the girls, rapes them while they are away from the house, and kills them. Coffey happens by the bodies and tries to heal them, but it’s too late. When Paul shares his findings with the rest of the guards, they realize that it is too late for Coffey to get a new trial. In the racial climate of the period, it is unlikely for a black man to receive a retrial, and, without Wharton, there is no way to show the public that he is the real killer. When they receive an official date of execution for Coffey, they realize they have no choice but to execute him, despite being aware of his innocence. When they inform Coffey of this, he tells them he is tired from holding the sadness of the world and is ready to go. He touches Paul one last time, transferring some of his vitality to him. At last, with grievous hearts, the guards send Coffey to his death.

Years later, Paul shares the written account of this story with Elaine. He reveals that Mr. Jingles, the pet mouse of executed inmate Delacroix, has been alive all this time, and living in a shed behind Georgia Pines. Coffey’s touch has extended the life of both Paul and Mr. Jingles. When Mr. Jingles ends up at Georgia Pines one day, Paul takes it as a sign that the end of his long life is near and that he must share Coffey’s story.

In the last chapter, Paul reveals the moments following the tragic Greyhound accident that led to the death of his wife, Janice. He realizes Coffey has saved him that day while also leaving him with the burden of survival. Coffey’s gift extends Paul’s life, but he has to watch people he loves die around him. Eventually, Elaine, the only one left who knows his story, passes away, too, leaving him all alone.