The Natural is the story of Roy Hobbs, a young baseball player whose promising career is derailed by a sudden shooting. The shooter, a mysterious woman, sends Hobbs careering out of control as he struggles to define himself outside the context of baseball and simultaneously strives to reenter the field of competitive play. In the end Hobbs is able to return to the game, but his career is short-lived and he soon becomes corrupt and finds himself ejected and stricken from all records.
Nineteen-year-old Roy Hobbs is traveling by train to Chicago with his manager Sam to tryout for the Chicago Cubs. Other passengers include sportswriter Max Mercy, Walter "The Whammer" Whambold, the leading hitter in the American League and three-time American League Most Valuable Player (based on Babe Ruth), and Harriet Bird, a beautiful but mysterious woman. The train makes a quick stop at a carnival along the rail where The Whammer challenges Hobbs to strike him out. Hobbs does just that, much to everyone's surprise and The Whammer's humiliation. Back on the train Harriet Bird strikes up a conversation with Hobbs, who never suspects that Bird has any ulterior motive. In fact, she is a lunatic obsessed with shooting the best baseball player. Her intended target was Whammer, but after Hobbs struck him out, her attention shifts to him.
In Chicago, Hobbs checks into his hotel and promptly receives a call from Bird, who is also staying there. When he goes down to her room, she shoots him in the stomach.
The novel picks up 15 years later in the dugout of the New York Knights, a fictional National League baseball team. The team has been on an extended losing streak and manager Pop Fisher's and assistant manager Red Blow's careers appear to be winding to an ignominious end. During one losing game, Roy Hobbs emerges from the clubhouse tunnel and announces that he is the team's new right fielder, having just been signed by Knights co-owner Judge Banner. Both Pop and Red take Hobbs under their wing, and Red later tells Hobbs about Fisher's plight as manager of the Knights. The Judge wants to take over Pop's share in the team but cannot do that until the current season ends and provided the Knights fail to win the National League pennant.
Being the newest player, Roy has a number of practical jokes played upon him, including the theft of his "Wonderboy" bat. Once Roy gets his first chance at bat, however, he proves to be a true "natural" at the game. During one game, Pop substitutes Hobbs as a pinch hitter for team star Bump Baily. Pop is disappointed with Baily, who has not been hustling and decides to teach him a lesson by pinch-hitting for him. Pop tells Roy to "knock the cover off of the ball." Roy literally does that—hitting a triple to right field. A few days later, a newly-hustling Bump attempts to play a hard hit fly ball. He runs into the outfield wall, later dying from the impact. Roy permanently takes over Bump's position.
Max Mercy reappears, searching for details of Hobbs' past. Hobbs remains quiet even after Mercy offers five thousand dollars, telling him that, "all the public is entitled to is my best game of baseball." At the same time, Hobbs has been attempting unsuccessfully to negotiate a higher salary with the judge, arguing that his success should be rewarded. Mercy introduces Hobbs to bookie Gus Sands, who is keeping company with Memo Paris, Pop's niece. Hobbs has been infatuated with Memo since he came to the Knights. Hobbs' magic tricks appear to impress her.
Max Mercy writes a column about the judge's refusal to grant Hobbs a raise, and a fan uprising ensues. Hobbs, however, is more occupied with Memo and attempts to further their relationship. Pop warns Hobbs about Memo's tendency to impart bad luck on the people she associates with. Hobbs dismisses the warning, but soon after, he falls into a hitting slump. Numerous attempts to reverse it fail until he finally hits a home run during a game where a mysterious woman rises from her seat. Before Hobbs can see who she is, she has left. Roy eventually meets her, Iris Lemon, and proceeds to court her. Upon learning she is a grandmother, however, he loses interest and returns his attention to Memo Paris.
Memo rebuffs Roy's advances; Hobbs continues to play brilliantly and leads the Knights to a 17-game winning streak. With the Knights one game away from winning the National League pennant, Roy attends a party hosted by Memo where he collapses and awakens in the hospital. The doctor says he can play in the final game of the season, but must retire after that if he wants to live. Hobbs wants to start a family with Memo and realizes he will need money.
The judge offers Hobbs a bribe to lose the Knight's final game. Hobbs makes a counter-offer of $35,000, which is accepted. That night, unable to sleep, he reads a letter from Iris. After seeing the word 'grandmother' in the letter, he discards it. He plays the next day and while at-bat, fouls a pitch into the stands that strikes Iris, injuring her, and splits the Wonderboy bat in two lengthwise. Iris tells Roy that she is pregnant with his child, and now he is determined to do his best for their future. At the end of the game, with a chance to win it, Hobbs, now trying to win, comes to bat against Herman Youngberry, a brilliant young pitcher very similar to Hobbs' at the same age. Youngberry strikes out Hobbs, ending the game and the season for the Knights. As he sits bemoaning the end of the season and possibly his career, Mercy rediscovers the shooting and also finds out that Hobbs was paid to throw the game. If this report from Mercy is true, Roy Hobbs will be expelled from the game and all of his records removed.