In a Louisiana assisted-living home in 1999, Paul Edgecomb begins to cry while watching the 1935 film Top Hat. His companion Elaine becomes concerned and Paul explains to her that the film reminded him of 1935, when he was a prison officer, and in charge of death row and the state's electric chair.

In 1935, Paul supervises Brutus "Brutal" Howell, Dean Stanton, Harry Terwilliger and Percy Wetmore at Cold Mountain Penitentiary on what they refer to as the "Green Mile", Death Row. Paul, suffering from a severe bladder infection, receives an extremely large, but mentally challenged, black man, John Coffey, into his custody; John had been convicted of raping and murdering two little white girls. Percy demonstrates a severe sadistic and bullying streak, but is beyond reproach; he is the nephew of Louisiana's First Lady. He is particularly abusive with inmate Eduard "Del" Delacroix; he breaks Del's fingers with his baton, steps on a pet mouse named Mr. Jingles, which Del had adopted, repeatedly calls him by a gay slur, and ultimately sabotages his execution by failing to soak the sponge used to conduct electricity to a condemned's head; Del's body explodes in flames and he dies screaming.

John begins to demonstrate supernatural powers; he cures Paul's bladder infection, resurrects Mr. Jingles, and heals Melinda Moores, wife of the prison's chief warden, of a brain tumor. This last affliction he releases into Percy, who under its influence shoots another prisoner, William Wharton, dead. Wharton had from the moment of his arrival been a troublemaker; he attacked the guards as he was being escorted into the block, made mischief on two occasions later which caused Paul to order him restrained in the block's padded cell, groped Percy briefly, and revealed psychically to John that he is in fact responsible for the crime for which John was unjustly condemned. John then reveals the story psychically to Paul, but in so doing releases his supernatural energy into Paul. Percy, meanwhile, is committed to the insane asylum which, ironically, Wharton had come from, and where he, Percy, was hopeful of getting a job.

John tells Paul, distraught over the notion of executing an innocent man, that he does in fact wish to die, as he views the world as a cruel place. Mentioning that he had never before seen a movie, John watches Top Hat with the other guards as a last request. That night, John is routinely executed, although he refuses the customary hood, as he is afraid of the dark. Paul concludes his story by telling Elaine that John's was the last execution that either he or Brutus supervised; they both took jobs in the juvenile system.

Elaine realizes that, since he had a grown son in 1935, Paul must be much older than he looks. Paul reveals that he is, in fact, 108 years of age, and not only is he still alive, so is Mr. Jingles, the mouse. The ending scene shows Paul as chief mourner at Elaine's graveside service, as he muses that if John's power could make a mouse live for as long as Mr. Jingles has, how much longer does he himself have left?

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