Thirty-one-year-old waitress and aspiring (but inexperienced) boxer Maggie Fitzgerald (Hilary Swank) tries to get aging trainer-coach Frankie Dunn (Clint Eastwood) to take her on, but where Maggie is unstoppably optimistic, Frankie is worn out, even burned out, and he repeatedly refuses. The two are brought together by Frankie's assistant, ex-fighter Eddie "Scrap-Iron" Dupris (Morgan Freeman). Freeman, whom the other characters call Scrap, narrates the film.

Maggie and Frankie have their ups and down, but Maggie rapidly becomes a formidable boxer, a great favorite with fans. Eventually she finds herself in the ring as challenger for the world welterweight title. The unscrupulous defender delivers an illegal punch to Maggie, resulting in a fall that leaves her paralyzed below the neck.

At this point the story turns from boxing to Maggie's injury, which is incurable and worsening because she is bedridden. After Maggie loses a leg to bed sores, she tells Frankie that she doesn't want to go on, and she asks him to put her out of her misery. Short as her career has been, she has known success and happiness beyond the dreams of her dirt-poor upbringing, and she wants to leave life while she can still remember those good things.

Frankie, a serious Catholic, has religious qualms. His priest tells him not to get involved. From his own point of view, Frankie has come to feel attached to Maggie, and at first he steadfastly refuses Maggie's request. Maggie, unable to act in any other way, bites her tongue violently in an attempt to bleed herself to death. After witnessing her agony, Frankie tells the priest that keeping Maggie close to him--in other words, not killing her--has come to feel like a sin. He then acts to rid himself of that sin. He covertly removes her air supply and then injects her with adrenalin. Frankie does not return to his gym, vanishing without a word.