Because of Winn-Dixie is a tale about a girl, her dog, and the quest for what truly matters in life. It is also a narrative about stories—tales of loss, love, and humor; accounts of holding on and letting go. Amid the sweltering humidity of a small-town in Florida, India Opal Buloni embarks on a journey toward friendship, love, understanding, and acceptance.

New to the town, Opal grapples with understanding and accepting why her mother left, questions why her father refuses to discuss her mother, and is in desperate need of a friend. She first finds companionship in a dog she considers "less fortunate" and names him after the place where they meet—Winn-Dixie. Because of this endearing dog's charm and loyalty, Opal soon encounters a variety of other lonely townspeople, each on their own quest to discover what the reclusive Gloria Dump calls "the most important thing."

Winn-Dixie wraps his love around each character, connects Opal with them, and, with Opal's help, brings them all together. Consequently, Opal learns invaluable lessons about life and love, but it takes both heartbreak and painful confrontation to pave the way toward healing before she realizes that letting go does not mean losing.