Eliza Thornberry plays with a family of cheetahs in Kenya after being left in charge of the cubs by their mother Akela. When Eliza strays far from the cheetahs' home, one of the cheetah cubs Tally is kidnapped by poachers in a helicopter. Eliza is determined to save the cub, which prompts her strict grandmother Cordelia to bring her to a boarding school in London as punishment for sneaking out to meet some wild animals. Upon arriving, Eliza discovers that her pet chimpanzee, Darwin, stowed away in her suitcase. He attempts to blend in but gets both him and Eliza in trouble.
After having a dream in which Shaman Mnyambo tells her to save Tally, Eliza and Darwin decide to return to Kenya. While taking a train from Nairobi, they encounter an injured male rhinoceros, who was shot at the river by the same poachers who kidnapped Tally. They save the rhino with the help of veterinarians Sloan and Bree Blackburn. Meanwhile, Eliza's older sister Debbie is left alone with her constantly feral adoptive younger brother Donnie at their RV, the Comvee, while their parents, Nigel and Marianne, go to film a solar eclipse at Tembo Valley. Eliza returns to the Comvee for supplies; after a small confrontation, Debbie pursues her, Darwin, and Donnie. Cordelia and her husband, Colonel Radcliffe, meet up with Nigel and Marianne to inform them of Eliza's escape, and they also begin searching for Eliza to force her back to school.
Darwin, Eliza, and Donnie meet a gorilla who mentions seeing people setting up a fence across Tembo Valley. Then, they run into the Blackburns again. Eliza concludes that the poachers are targeting an elephant herd traveling through the valley. Later, the trio finds Tally in the Blackburns' RV, exposing their true nature as the poachers. The Blackburns capture them and reveal the fence is electrified. Meanwhile, Debbie meets a local Mbuti boy named Boko, who is sent by his village elders to assist her. The two reach the Blackburns' RV, but Sloan holds Debbie hostage after she reveals she is Eliza's sister. When Sloan threatens to kill Debbie if Eliza doesn't tell him how she found out their decision, Eliza admits it was because of her ability to talk to animals. A storm arrives and takes away Eliza's powers while the Blackburns flee.
They reach Tembo Valley in time to see the elephant herd heading for the electric fence. When Eliza becomes doubtful of herself, Debbie reminds her that she has been helping animals long before gaining her powers, restoring her confidence. The Blackburns, riding their helicopter, order their men to set off explosives, scaring the elephants and making them charge toward the fence. Eliza triggers the fence's electricity prematurely, causing the herd to stop temporarily, and then convinces the lead elephant to turn around. Infuriated by this, Sloan throws Eliza into a river. He then attempts to shoot the elephants, but they pull the Blackburns' copter out of the air by its rope ladder and destroy it, causing him and Bree to fall. They survive the fall, but are apprehended by park rangers soon after as the eclipse ends. Eliza nearly drowns until she is saved by Shaman Mnyambo, who tells her she saved the elephants using her heart instead of her powers. As a reward, he gives her back her powers.
Eliza reunites with her family, who decide to lift Eliza's punishment and not to send her back to boarding school, while Boko returns to his village, keeping Debbie's watch as a memento. The Thornberrys return to the savanna, where Eliza reunites Tally with his family. Debbie is angered when Eliza tells her that she will turn into a baboon if she reveals her secret and, in the process, frightens a group of olive baboons Nigel and Marianne are filming. One of them activates the radio, which plays music that the Thornberrys and the primates dance to.
The film opened in the U.S. box office on December 20, 2002, and finished at #6 for the weekend, with $6 million for 3,012 theaters, for an average of $1,997 per venue. The film ended up with a modest $40 million domestically, partly because the film released two days after The Lord of the Rings: The Two Towers. Despite this, in light of generally favorable reviews, it managed to out-gross competing animated feature Treasure Planet, which grossed about $38 million domestically.
[first lines; narrating] I'm Eliza Thornberry, part of your average family. I've got a dad and a mom and a sister. There is Donnie, we found him. And Darwin, he found us. We traveled all over the world. See, my dad hosts…
Eliza
Grandma Cordelia: [after Akela the cheetah mother chases off a pack of gazelles] Does this sort of thing happen often?
Thornberrys: No.
Grandma Cordelia: [relieved] Thank goodness. [shockingly finds grubworms in her…
Eliza: [demanding] Give him back! [the unidentified male poacher shines a light on her] He's just a baby!
Nigel: [on radio] Deborah, we need you to bring the Comvee straight away!
Debbie: [through radio] I wish I could…
Jomo: Poachers are dangerous people.
Marianne: Eliza, are you listening?
Eliza: But the poacher was taking Tally!
Marianne: Who?…
Marianne: [flipping through the family photo album] We agreed when we took this job that we wouldn't split up the family. [closes the photo album] We'd keep the children with us on the road.
Nigel: I remember, dearest.…
Elizabeth, it's time for take-off. Kiss your natural wilderness girlhood goodbye!