Margaret “Maggie” Fitzgerald (Hilary Swank), a waitress from a Missouri town in the Ozarks, shows up in the Hit Pit, a run-down Los Angeles gym owned and operated by Frankie Dunn (Clint Eastwood), an old, cantankerous boxing trainer. Maggie asks Frankie to train her, but he initially refuses. Maggie works out tirelessly each day in his gym, even after Frankie tells her she’s “too old” to begin a boxing career at her age. Eddie “Scrap-Iron” Dupris (Morgan Freeman), Frankie’s friend and employee—and the film’s narrator—encourages and helps her.
Frankie’s prize prospect, “Big Willie” Little, signs with successful manager Mickey Mack after becoming impatient with Frankie rejecting offers for a championship bout. With prodding from Scrap and impressed with her persistence, Frankie reluctantly agrees to train Maggie. He warns her that he will teach her only the basics and then find her a manager. Other than Maggie and his employees, the only person Frankie has contact with is a local priest, with whom he spars verbally at daily Mass.
Before her first fight, Frankie leaves Maggie with a random manager in his gym, much to her dismay; upon being told by Scrap that said manager deliberately put her up against his best girl (coaching the novice to lose) to give her an easy win, Frankie rejoins Maggie in the middle of the bout and coaches her instead to an unforeseen victory. A natural, she fights her way up in the women’s amateur boxing division with Frankie’s coaching, winning many of her lightweight bouts with first-round knockouts. Since Maggie has earned a reputation for her KOs, Frankie must resort to bribery to get other managers to put their trainee fighters up against her.
Eventually, Frankie takes a risk by putting her in the junior welterweight class, where her nose is broken in her first match. Frankie comes to establish a paternal bond with Maggie, who substitutes for his estranged daughter. Scrap, concerned when Frankie rejects several offers for big fights, arranges a meeting for her with Mickey Mack at a diner on her 33rd birthday. Out of loyalty, she declines. Frankie begrudgingly accepts a fight for her against a top-ranked opponent in the UK, where he bestows a Gaelic nickname on her. The two travel to Europe as she continues to win; Maggie eventually saves up enough of her winnings to buy her mother a house, but her mother berates Maggie for endangering her government aid, claiming that everyone back home is laughing at her.
Frankie is finally willing to arrange a title fight. He secures Maggie a $1 million match in Las Vegas, Nevada, against the WBA women’s welterweight champion, Billie “The Blue Bear” Osterman, a German ex-prostitute who has a reputation as an unpunished dirty fighter. Overcoming a shaky start, Maggie begins to dominate the fight, but Billie knocks her out with an illegal sucker punch from behind after the bell rings to end the round. Before Frankie can pull the corner stool out of the way (which was inappropriately placed on its side by Frankie’s assistant), Maggie lands hard on it, breaking her neck and leaving her a ventilator-dependent quadriplegic.
Frankie is shown experiencing the first three of the five stages of grief: first seeking multiple doctors’ opinions in denial, then blaming Scrap in anger, and later trying to bargain with God through prayer.
In a medical rehabilitation facility, Maggie looks forward to a visit from her family, but they arrive accompanied by an attorney; their only concern is to transfer Maggie’s assets to them. She orders them to leave, threatening to sell the house and inform the IRS of her mother’s welfare fraud if they ever show their faces again.
As the days pass, Maggie develops bedsores and undergoes an amputation for an infected leg. She asks a favor of Frankie: to help her die, declaring that she got everything she wanted out of life. A horrified Frankie refuses, and Maggie later bites her tongue repeatedly in an attempt to bleed to death, but the medical staff saves her and takes measures to prevent further suicide attempts. The priest Frankie has harassed for 23 years, Father Horvak, warns him that he would never find himself again if he were to go through with Maggie’s wishes.
Frankie sneaks into the hospital one night, unaware that Scrap is watching from the shadows. Just before administering a fatal injection of adrenaline, he finally tells Maggie the meaning of a nickname he gave her, Mo Chuisle (misspelled in the film as “mo cuishle”): Irish for “my darling, and my blood” (literally, “my pulse”). He never returns to the gym. Scrap’s narration is revealed to be a letter to Frankie’s daughter, informing her of her father’s true character. The last shot of the film shows Frankie sitting at the counter of a diner where Maggie once took him, and after having a homemade lemon meringue pie with her, said: “Now I can die and go to heaven.”