In 1932, the dawn of the Great Depression, a young baseball fan Yankee Irving (Jake T. Austin), whose father Stanley (Mandy Patinkin) works as a janitor for New York City's Yankee Stadium, dreams of playing for the Yankees but can't even play sandlot baseball well enough to avoid being picked last. One day beside the sandlot, he finds a talking baseball he names Screwie (Rob Reiner).
While father and son are in the stadium, a thief steals Babe Ruth's famous bat Darlin' (Whoopi Goldberg). Yankee's father is blamed and accordingly fired. The true thief is Lefty Maginnis (William H. Macy), a pitcher for the Chicago Cubs. Lefty works for Cubs owner Napoleon Cross (Robin Williams), who desires to see the Cubs defeat the Yankees during the 1932 World Series.
Stealing the bat back, Yankee decides to return it to Ruth—and thereby exonerate his father—by journeying across the country to Chicago, where the next World Series' games will be played. Darlin' is able to speak, as does her counterpart Screwie, who she constantly argues and bickers with (though near the end, they finally become friends). Much of the plot is driven by Lefty's comic attempts to retrieve the bat from Yankee, withslapstick results. Other scenes involve Yankee meeting others who will help him in his quest: several hobos (Ed Helms); Marti (Raven-Symoné), an African American girl; her baseball player father Lonnie Brewster (Forest Whitaker); and in Chicago, Babe Ruth himself (Brian Dennehy).
A series of improbable coincidences allows Yankee himself to bat for the Yankees, resulting in the archetypal home run (technically, a series of errors after an infield pop-up that allow him to round the bases). This restores the morale of the Yankees, who score 7 more runs to take the lead and win the World Series. Cross tries to talk Babe Ruth out of accepting the victory, saying that Yankee is too young to be a counting player. This leads to the arrest of Cross, and also Lefty. Yankee also successfully exonerates his father. Yankee returns home, now knowing what is truly important in baseball.