Set in South Africa, the story begins with a cheetah cub orphaned after his mother is killed by lions. The cub is found on the side of the road by a young boy named Xan and his father Peter. Initially reluctant to take in a wild animal, Peter agrees to let Xan take care of the cub. They name him Duma, the Swahili name for cheetah. Over the years, Duma becomes a part of the family, closely raised by Xan. As he nears adulthood, Peter and Xan decide to teach Duma how to run by having him chase alongside Peter's motorcycle, which can barely keep up.
But with Duma almost fully grown, to Xan's dismay, his father tells him that it is time to take his friend to his real home before he grows too old to survive in his native habitat. His father says to Xan, "Duma has to live the life he was born to—or he'll never be fully alive."
> Duma has to live the life he was born to—or he'll never be fully alive.
Xan reluctantly agrees, but their plans are put on hold when his father suddenly falls ill and dies and Xan and his mother Hope Davis must move to Johannesburg. Duma comes with them, which wreaks havoc on their life in the city. Xan's aunt is terrified of Duma, who likes to sneak up and surprise her, and when Duma escapes and pays a disastrous visit to Xan's school, the two of them must flee the city to keep Duma from being put into captivity. Not knowing where to go, Xan gets an idea—he'll carry out the plan his dad had outlined, taking Duma home in the neighboring country of Botswana, over the scorching Makgadikgadi Salt Pans, through the Okavango Delta and into the Erongo Mountains.
Xan begins to drive to his destination in his father's old motorcycle, with Duma in the sidecar. After running out of fuel and water in the grasslands, they find some shade underneath a crashed airplane. There, they are confronted by Ripkuna, a mysterious drifter on a journey of his own. While Xan isn't at all that sure he can trust Rip, he agrees to go with him. Xan manages to turn the immobile motorcycle into a desert sailboat out of a parachute from the plane wreck. The trio make their way until they encounter the untraversable scrub brush of the Kalahari Desert and must abandon the motorcycle. While trying to find shelter, Rip is trapped in an abandoned diamond mine by a cave in, and Xan decides to leave him, as he suspects that he has been leading him to town instead of the jungle to sell Duma and collect a reward for finding him. However, when Duma is caught in a trap and Xan is knocked unconscious by a boar, Rip rescues both of them, having escaped the mine through a ventilation shaft.
Soon, they reach the Okavango Delta, where Xan is attacked by the deadly wildlife and the churning rapids of the Thamalakane River, but it's too late for him to turn back now. Xan, Rip and Duma press through the Okavango, and finally the Erongo Mountains, on the border of Botswana and Namibia are in sight. However, once they get there, Xan is suddenly set upon by a swarm of tsetse flies. To protect him from their lethal bite, Rip huddles over Xan and is bitten by hundreds of flies. He soon develops sleeping sickness, and Xan takes him to a nearby village where he can be cared for; it is soon revealed that those taking care of him are actually his own family. Later that night, outside the village, Duma is out on his own and starts calling out into the mountains. Duma finds another cheetah calling to him, and they bond rather quickly. It is never explained whether this is another male cheetah, or is in fact one of Duma's siblings. Xan hears this activity, and realizes that this is where he and Duma must part. Xan says goodbye to Duma, and Duma comes to Xan and says a final goodbye, and goes back to play with his new friend. Xan returns to Rip in the village. Before the credits, it shows Xan being reunited with his mother.
