In the Australian Outback, a young boy named Cody rescues and befriends a rare giant eagle named Marahute, who shows him her nest and eggs. Later on, the boy unknowingly falls into an animal trap set by Percival C. McLeach, a local poacher wanted by the Australian Rangers. When McLeach finds one of the eagle's feathers on the boy's backpack, he is instantly overcome with excitement, for he knows that catching an eagle that size would make him rich because he had caught one before, which was Marahute's mate. McLeach throws Cody's backpack to a pack of crocodiles in order to trick the Rangers into thinking that Cody was dead, and kidnaps him in his attempt to force him to reveal the whereabouts of Marahute.
A mouse, the bait in the trap, runs off to alert the Rescue Aid Society. A telegram is sent to the Rescue Aid Society headquarters in New York City, where Bernard and Miss Bianca, the RAS' elite field agents, are assigned to the mission, despite Bernard's attempts to propose marriage to Bianca. They go to find Orville the albatross who aided them previously, but instead find his brother Wilbur. Bernard and Bianca convince Wilbur to fly them to Australia to save Cody. In Australia, they meet Jake, a hopping mouse who is the RAS' local regional operative. Jake becomes infatuated with Bianca and starts flirting with her, despite Bernard's chagrin. He serves as their "tour guide" and protector in search of the missing boy.
At the same time, Wilbur is immobilized when his spinal column is bent out of its natural shape, convincing Jake to send him to a nearby hospital run by mice. Wilbur, terrified of the surgical equipment the doctor intends to use (including a chainsaw), refuses to undergo surgery and is forced to flee. His back is unintentionally straightened by the efforts of the mouse medical staff preventing him from escaping through a window. Cured, Wilbur departs in search of his friends. At McLeach's ranch, Cody has been thrown into the dungeon with several of McLeach's imprisoned animals for refusing to give up Marahute's whereabouts. Cody tries to free himself and the animals using various objects tied together with a hook on the end, but he is thwarted every time by Joanna, McLeach's pet goanna. Realizing that Marahute's eggs are Cody's weak spot, McLeach tricks Cody into thinking that Marahute has died, causing Cody to lead him straight to Marahute's nest.
Bernard, Bianca, and Jake, knowing that Cody is about to fall for a trap, jump onto McLeach's Halftrack to follow him. At Marahute's nest, the three mice try to warn Cody that he has been followed; for just as they do, McLeach arrives and captures Marahute, along with Cody, Jake, and Bianca. Following McLeach's orders, Joanna tries to eat Marahute's eggs, but realizes they are actually egg-shaped rocks. Frightened that McLeach might be angry with her, Joanna drops the stones over the cliff instead. When she leaves, Bernard crawls out of the nest with the hidden eggs, grateful that Joanna fell for the trick. Just then, Wilbur arrives at the nest, whereupon Bernard convinces him to sit on the eagle's eggs, so that Bernard can go after McLeach. Enraged by Cody's interference, McLeach takes his captives to Crocodile Falls, where he ties Cody up and hangs him over a group of crocodiles in attempts to feed him to them. But Bernard, riding a wild razorback pig he had tamed using a horse whispering technique that Jake used on a snake earlier, follows and disables McLeach's vehicle.
McLeach then tries to shoot the rope holding Cody above the water. To save Cody, Bernard tricks Joanna into crashing into McLeach, causing them to both fall into the water. This causes the crocodiles to turn their attention from Cody toward McLeach and Joanna, while behind them the badly damaged rope holding Cody breaks apart. McLeach fights and fends off the crocodiles, but although Joanna manages to reach the shoreline, McLeach is swept over the waterfall to his death. Bernard dives into the water to save Cody, but every time he fails. His actions, however, buy Jake and Bianca enough time to free Marahute so they can save both Cody and Bernard.
Bernard, desperate to prevent any further incidents, proposes to Bianca, who eagerly and happily accepts while Jake salutes him with a newfound respect. All of them depart for Cody's home. Back at the nest, Marahute's eggs finally hatch, much to Wilbur's dismay.
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