Lady Alexandra pleads with the British Museum to allow her to look for the Percy Fawcett camp in the Amazon jungle. She is allowed to go.
Mr.Hooten, an American thief, is in the Amazon Basin, trying to sell a stolen diamond to some nefarious characters. He swalows the diamond and tries to escape, but the bad guys tie him to his horse Clara, and he is dragged into the jungle.
He smashes into a native tribe, and a gold skull accidently falls into his hands. He is captured and knocked out by the tribe.
He awakes to find he's tied up, hanging from a pole, with Lady Alex next to him. The native are also cooking and eating his horse Clara. Alex is very angry, and tells him they are both in mortal danger because of his actions.
She tells Hooten the only way they can escape death is for him to challenge and defeat their strongest warrior. He wins, but also secretly steals the gold skull. Hooten and Alex run for their lives in the jungle. They reach her boat and escape down the Amazon.
The Museum is concerned, since they've lost contact with Alex. Hooten and Alex set up camp, and argue over what to do next. Alex demand to find Fawcett, and will only return Hooten to an outpost after her quest. He reluctantly agrees.
Alex follows an ancient map and finds Fawcett's camp, complete with his well preserved skeleton.
Alex carefully catalogs and bags the artifacts. The next morning, Alex finds a map to Eldorado, the Lost City of Gold clutched in the hand of Fawcett.
Hooten and Alex come to an agreement to search fpr the city, but must go an outpost on the river to get supplies.
Alex gets in touch with her guide Pascal, and shows him a picture of the treasure map via Skype. Pascal copies the map and lies to his Museum bosses about his contact with Alex.
Alex discovers the god skull, and she argues with Hooten about their partnership, storming off into the jungle, only to slip and fall, hanging by a tree over a huge ravine. Hooten tries to save her, but thet both fall into the ravine, tumbling down to the floor of the jungle, where they stumble upon Eldorado.
Pascal finds them, and shoots Hooten in the shoulder. He ties them up and starts stealing all the gold he can carry.
Pascal takes Alex hostage on his helicopter, leaving Hooten for dead. Hooten escapes his bonds, and jumps on the chopper as it flies away. He fights Pascal inside the chopper. Hooten and Alex jump from the chopper inot the river, seconds before the chopper crashes, killing Pascal.
Back in England, the exhibit is a success, with Alex's friends asking about Hooten.
Back in Rio, Hooten sells the stolen diamond, and takes almost all the money to an orphanage to make an anonymous donation.