Somewhere southeast of Australia rest three little islands, teeming with wildlife. Two humans, however, have been experimenting with the local furry creatures in order to form a destructive and evil army of mutants. Doctor Nitrus Brio creates a machine called the Evolvo-Ray, an invention capable of turning animals anthropomorphic, but his ever pushy employer (and main series antagonist) takes the credit. One night in his castle, Doctor Neo Cortex has just captured two bandicoots; one male and one female. They are both put under the Evolvo-Ray and both work successfully.

Dr. Cortex plans to make the male the leader of his Cortex Commandos for world domination and inserts the evolved male (Crash) into his patented Cortex Vortex, a mind-controlling device designed to brainwash mammals and turn them into evil henchmen, even though Dr. Brio warns Cortex that the Vortex is not ready. Crash turns out to be an utter failure and is rejected by the Vortex. Crash also meets a floating tiki mask known as Aku Aku, who aids crash by giving him extra resistence(hit points) and sometimes invincibility.

Knowing full aware that Crash will come back for Tawna, Cortex sends out his best henchmen (one of them also being a failed experiment) to stop him. Crashandtwana1 Crash and Tawna finally together. Cortex's plan, however, is foiled when Crash eventually reaches his toxic waste factory and shuts it down when battling the C.E.O. and Cortex's bodyguard, Pinstripe. Crash soon enters Cortex's sinister castle.