In South Africa within the Great Karoo, a half-striped zebra named Khumba (Jake T. Austin) is born into an insular isolated herd of all-striped zebras where his mother is Lungisa (Anika Noni Rose) and his father is Seko (Laurence Fishburne). Rumors that the strange foal is cursed spread and before long he is blamed for the drought that sets into the Great Karoo. As he matures, Khumba is picked on and remains ostracized by most of the herd with the exception of Tombi (AnnaSophia Robb), a young female zebra friend close in age – whom Khumba has a crush on – and uncomfortable in the herd due to her tomboyish manners.
When a mystical African mantis (Adrian Rhodes) appears to Khumba, he draws a map to what could be interpreted as either water or stripes between it. Khumba jeopardizes the herd and gets into trouble when he attempts to admit several gemsbok (Nhlanhla Mkhwanazi and Anele Matoti) into the watering-hole enclosure when their wise elderly healer (Sindiwe Magona) needs water. He also nearly admits the ferocious half-blind African leopard Phango (Liam Neeson) who warns Mkhulu (Ben Vereen) that he and his zebra herd can’t stay in their enclosure forever. Seko berates and scolds Khumba for putting the herd at risk and for the next week, he’ll drink half of his rations. Lungisa tells the story of how a white horse got its stripes by swimming in a magic river and other horses wanted to have stripes like him, making the zebra we know today. Shortly after, Lungisa succumbs to her disease and dies. Then, Khumba leaves the confines of his home knowing that he cannot survive in the herd where is viewed as only “half-a-zebra” even to his father.
Khumba ventures beyond the fence and encounters an opportunistic African wild dog named Skalk (Steve Buscemi) who nearly leads the unsuspecting zebra to his doom when Skalk’s pack try to eat him. He is saved by a maternal wildebeest named Mama V (Loretta Devine) and a flamboyant British ostrich named Bradley (Richard E. Grant). Mama V is a self-confessed free spirit who does not want to be the average stay-at-home mom, like other wildebeest. Ironically, she mothers Bradley who possesses a histrionic diva-esque attitude. The duo join Khumba on his quest in the hope that their own search for a safe waterhole is over.