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In 2029, mutants have almost stopped being born and the X-Men are gone. Logan is old, limping, drinking too much and working as a limo driver in El Paso, Texas. His healing factor is failing because the adamantium in his skeleton is poisoning him. Across the border, in an abandoned smelting plant in Mexico, he hides Charles Xavier, who is over 90 and has dementia. The Professor's seizures turn into telepathic blasts that freeze everyone nearby. Caliban, a mutant who can track other mutants, helps look after him.
A nurse named Gabriela offers Logan money to drive a girl, Laura, to a place called Eden on the Canadian border. Logan says no, then yes, and finds Gabriela dead. Laura is already hiding in his car. Right behind her come Donald Pierce and his Reavers, cybernetic mercenaries working for a company called Transigen. They grab Caliban. Laura shows what she is: claws in her hands and feet, fast healing and a rage just like Logan's. A video on Gabriela's phone reveals Transigen was breeding kids from mutant DNA to use as weapons. Laura was made from Logan's DNA. She's his daughter.
Logan, Charles and Laura hit the road. At a hotel in Oklahoma City, one of Charles's seizures freezes the whole building, and Logan has to kill the soldiers to get out. Logan learns that Eden comes straight out of an X-Men comic book Laura carries around. The three stop to help farmer Will Munson's family and share a dinner, the closest thing to a normal life Charles has had in years. That night, Dr. Zander Rice unleashes X-24, a young, feral clone of Logan. It kills Charles and the Munsons. Caliban blows himself up with grenades rather than keep helping the hunters.
Wounded, Logan wants to quit, but Laura gets him to the comic's coordinates in North Dakota. Other kids who escaped Transigen are there, ready to cross the border. Logan gives them the money and plans to leave. When the Reavers arrive, he takes a dose of the leftover serum, fights like he used to and kills Rice. The kids turn their powers on the soldiers, and Pierce dies.
X-24 impales Logan on a tree branch. Laura shoots the clone with the adamantium bullet Logan had been carrying for years. Logan dies holding his daughter's hand, saying so this is what it feels like. At the burial, Laura recites the speech from the movie Shane and tilts the cross sideways into an X. The kids head on to Canada.