Léon Montana (Jean Reno) is an Italian hitman (or "cleaner", as he refers to himself) living a solitary life in New York City's Little Italy. His work comes from a mafioso named Tony (Danny Aiello). Léon spends his idle time engaging in calisthenics, nurturing a houseplant, and watching old films.
One day, Léon meets Mathilda Lando (Natalie Portman), a lonely 12-year-old girl. Mathilda lives with her dysfunctional family in an apartment down the hall, and has stopped attending class at her school for troubled girls. Mathilda's abusive father (Michael Badalucco) attracts the ire of corrupt DEA agents, who have been paying him to stash cocaine in his apartment. After they discover he has been cutting the cocaine to keep for himself, DEA agents storm the building, led by sharply dressed drug addict Norman Stansfield (Oldman). During the raid, Stansfield quickly becomes unhinged and murders Mathilda's entire family while she is out shopping for groceries. When Mathilda returns, she realizes what has happened just in time to continue down the hall to Léon's apartment, who hesitantly gives her shelter.
Mathilda quickly discovers that Léon is a hitman. She begs him to take care of her and to teach her his skills, as she wants to avenge the murder of her four-year-old brother. At first, Léon is unsettled by her presence, but he eventually trains Mathilda and shows her how to use various weapons. In exchange, she runs his errands, cleans his apartment, and teaches him how to read. In time, the pair forms a close bond. Mathilda often tells Léon she is in love with him, but he refuses to reciprocate.
When Léon heads out for an apparent assignment, Mathilda fills a bag with guns from Léon's collection and sets out to kill Stansfield. She bluffs her way into the DEA office by posing as a delivery girl, only to be ambushed by Stansfield in a bathroom; one of his men arrives and announces that Léon had just killed one of the corrupt DEA agents in Chinatown that morning. Léon, after discovering her plan in a note left for him, rescues Mathilda, shooting two more of Stansfield's men in the process. An enraged Stansfield confronts Tony, who is violently interrogated for Léon's whereabouts.
As Mathilda and Léon recover from the ordeal, Mathilda attempts to seduce Léon. Léon refuses, instead opening up about how he became a cleaner; when Léon was young in Italy, he was in love with a girl from a wealthy family. The two made plans to elope, but when the girl's father discovered their relationship, he killed her out of anger and escaped justice. Léon killed the man out of revenge and fled to New York, where he met Tony and trained to become a cleaner.
Later, while Mathilda returns home from grocery shopping, a NYPD ESU team sent by Stansfield captures her and attempts to infiltrate Léon's apartment. Léon ambushes the ESU team and rescues Mathilda. Léon creates a quick escape for Mathilda by smashing a hole in an air shaft; he then reassures her, tells her that he loves her, and thanks her for giving him "a taste for life", moments before the police blow up the apartment. In the chaos that follows, Léon sneaks out of the building disguised as a wounded ESU officer; he goes unnoticed save for Stansfield, who follows him and shoots him in the back. As he is dying, Léon places an object in Stansfield's hands that he says is "from Mathilda" before succumbing to his wounds; Stansfield discovers that it is a grenade pin. He then opens Léon's vest to find a cluster of active grenades which detonates, killing Stansfield.
Mathilda goes to Tony, as Léon had instructed her to do before he died. Tony tells Mathilda he had been instructed by Léon to give his money to her if anything happened to him; he offers to hold it and provide the money on an allowance basis. Mathilda returns to school and meets the headmistress, who readmits her after Mathilda reveals what had happened to her. She then walks onto a field near the school to plant Léon's houseplant, as she had told Léon he should, to "give it roots".
- Jean Reno as Leone "Léon" Montana
- Natalie Portman as Mathilda Lando
- Gary Oldman as Norman Stansfield
- Danny Aiello as Tony
- Michael Badalucco as Mathilda's father
- Ellen Greene as Mathilda's stepmother
- Elizabeth Regen as Mathilda's sister
- Peter Appel as Malky
- Joseph Malerba as Stairway Swat
- Maïwenn as The Blond Babe
- George Martin as The Hotel Receptionist
- Jean-Hugues Anglade as Cameo