After being accidentally left behind by his circus crew, a young zebra (voice of FRANKIE MUNIZ) finds himself in the custody of Nolan Walsh (BRUCE GREENWOOD), a farmer whose teenage daughter, Channing (HAYDEN PANETTIERE), instantly adores and names the young foal Stripes. After she convinces her dad to allow her to keep him, Stripes ends up in the barn where he meets a number of other talking animals. There's Shetland Pony Tucker (voice of DUSTIN HOFFMAN), his goat friend Franny (voice of WHOOPI GOLDBERG); Reggie (voice of JEFF FOXWORTHY), the scatterbrained rooster; and the porch-bound bloodhound Lightning (voice of SNOOP DOGG). Eventually joining them is Goose (voice of JOE PANTOLIANO), a mob pelican who's hiding out from the big city.
While there are no local mobsters for him to worry about, the local power comes in the form of Clara Dalrymple (WENDIE MALICK) whose nearby estate trains thoroughbreds such as Sir Trenton (voice of FRED DALTON THOMPSON) and his offspring Trenton's Pride (voice of JOSHUA JACKSON). Clara doesn't care for Nolan, her former trainer, and the various animals on her land make fun of Stripes who doesn't realize he's a zebra and not a horse.
That is, except for young mare Sandy (voice of MANDY MOORE) who's taken a liking to the now three-year-old "teenager" who dreams of one day racing in the prestigious Kentucky Open. That seems like a long shot since Nolan won't even let Channing ride him -- for fear of losing her as he did Channing's mother years ago -- but when longtime track regular Woodzie (M. EMMET WALSH) clocks him in an impromptu sprint, things begin to look up.
With Clara allowing the zebra into the Open as a joke, Noland, Channing and even Tucker start training Stripes in how to race. With the aid of the comedy horsefly duo of Buzz (voice of STEVE HARVEY) and Scuzz (voice of DAVID SPADE), the zebra sets out to overcome various external obstacles and self-doubts to realize his dream.