Henry Rowengartner (Nicholas), a 12-year-old Little Leaguer, has dreams of playing in the major leagues. One day, Henry breaks his arm trying to catch a fly ball and has to wrap it in a cast. When the cast is removed, he celebrates the occasion by attending a Chicago Cubs game in the bleachers of Wrigley Field with his friends. One of his friends catches a visiting team home run ball and gives it to Henry to throw it back. He shocks the crowd by throwing it all the way back to home plate. His doctor explains that he can throw this far and this hard because the tendons in his arm have healed "a little tight."
The Cubs, in need of a "miracle" to save the poor-performing team, sign Henry to a contract, making him the youngest-ever major leaguer. Henry's mother's boyfriend, Jack, whom Henry dislikes, signs on as Henry's manager. When Henry first enters the locker room he is awestruck to be in the presence of some of his heroes, including Chet Stedman (Busey), an irascible pitcher in the twilight of his career who suffers from shoulder pain on the mound and frequently makes grunting or painful sounds such as "EEEYAH!" after each pitch.
Henry's first appearance as a relief pitcher comes against the New York Mets which proves to be disastrous. In that game, he gives up a home run to Alejandro "Butch" Heddo. Chet Steadman, gives Henry some advice on becoming a better major-league pitcher, including using the "have to". After that, the Cubs keep winning, and he keeps earning saves.
In one game at Dodger Stadium, Henry is shocked to learn that he is going up to bat (as National League pitchers must bat). Although Henry is very nervous at the plate, the pitcher (frustrated by Henry's tiny strike zone) walks Henry on four straight pitches. On the last pitch, Henry closes his eyes and swings at the ball after the ball is already in the catcher's mitt, leading announcer John Candy to say "Hank took a big rip at that one, but the ump had already made the call". Once Henry arrives at first base, he begins taunting the pitcher (using one of his most famous quotes, "Pitcher's got a big butt! Pitcher's got a big butt!" with the pitcher actually checking his butt!). The pitcher then tries to pick Henry off but overthrows it and Henry goes to second where he continues teasing the pitcher and the second baseman. He and the next batter would later score the go-ahead runs despite the batter nearly passing Henry on the bases.
Henry endorses several products, including Diet Pepsi, where he replaces Ray Charles in the popular "You Got the Right One, Baby" campaign. However, he and Jack have a falling out when Henry finds out that he has been sold to the New York Yankees. Henry fires Jack. Henry's mother also breaks up with Jack over his obsession with making money off of Henry. However, as for the trade to the Yankees, it turns out that the deal had never been officially made, and Henry continues pitching for the Cubs.
The final game of the season pits the Cubs against the Mets. Before the game, Henry announces to the Cubs' owner that it will be his last game. He also tells the owner about Jack and General Manager Larry Fisher's scheme to try to sell Henry to the Yankees. Later it is shown that Larry has in response been demoted down to hot dog vendor. It also proves to be Steadman's last game, as his arm is dramatically blown out (accompanied with an intense guitar riff) on his last pitch in the seventh inning, forcing Henry to step in to finish the game.
Henry completes the seventh and eighth innings without trouble. However, as Henry walks out to the field in the ninth, he trips on a baseball and falls on his side. He is all right, but he can no longer throw a 100-mile-per-hour fastball. After letting his teammates know what happened, Henry instead must rely on his wit with their help. He intentionally walks the first two consecutive Mets batters. He also gets the first runner out by doing a hidden ball trick; he sneaks the ball to his first baseman and gets the Mets player out. He dares the second runner to run to second base; Henry gets him out by running and tagging him.
Finally, Henry faces his old nemesis, Alejandro "Butch" Heddo. Determined to get his ultimate revenge, Henry throws a changeup for the first strike. Heddo is not fooled with Henry's next pitch and he sends it skyrocketing toward home run territory. However, it barely sails past the foul pole. Rattled, Henry bides his time and peels back the mitt to find his mother's name on it. Surprised, he turns to his mother in the stands, who mouths, "Float it." Regaining his confidence, he throws an Eephus pitch. A shocked Heddo swings and misses for the final out, who then throws a tantrum right at home plate while the Cubs celebrate winning the division. Thanks to Henry, the Cubs win their division title and go on to win the World Series.
At the end of the movie, Henry is playing Little League again, with his mother as the new coach and Chet Steadman as her assistant. Henry flashes a ring with a blue stone in it. The inscription reads: WORLD SERIES CHAMPIONS.