Somewhere in a small Australian archipelago, the evil scientist Dr. Neo Cortex is snatching marsupials off of their natural habitats to create an army of super animals. He intends to take over the World and shut up all those who laughed at his ideas. To do this, he has requested the help of Dr. Nitrus Brio, a long-time friend, and a bit of a rival. Brio created the first fully functional Evolvo-Ray, a machine capable of increasing intelligence in animals and giving them human-like qualities. In short, it evolves any animal that gets zapped with it. After the evolution, one final step is added: the exposure of the animal to the Cortex Vortex, a mind-controlling device created by Dr. Cortex himself.
With the plan established and everything ready, Dr. Cortex gives the experiment a green light and starts evolving and brainwashing the marsupials. Amidst these marsupials is Crash, an Eastern Barred Bandicoot, and the general-to-be in Cortex's marsupial army. Though the evolution goes fine on Crash, the Cortex Vortex soon rejects him for his kind nature. This makes Cortex throw Crash away as garbage - his second big mistake of the day. Before Crash got the boot, he met a charming she-bandicoot named Tawna, and he's not going to give up on her without a fight, even if he has to confront the evil doctor himself.
Crash is washed away by the sea, drifting unconsciously and eventually arriving to what they call N. Sanity Island. Protecting this island and the whole archipelago is the spirit of Aku Aku, a once great and benevolent witch doctor. When he learns that Crash is out to defeat Cortex (and thus, stop his pollution), Aku Aku decides to help him. Aku Aku protects and communicates with Crash through the aid of a special mask. They both set out to stop Cortex's plans, and this marks the beginning of an endless quarrel between a scientist and his creation.