Tired of endlessly doing battle with meddling bandicoots, the nefarious Dr. Neo Cortex shrinks the entire Earth, and Crash and Coco along with it, to the size of a wumpa fruit. Luckily, Coco invents a machine to reverse the effects, but she needs crystals from around the world to power it. Crash must retrieve the crystals to help return the entire planet to its natural state. Experience Crash's biggest adventure yet, with gameplay modes ranging from side-scrolling to 3D chase levels to aerial dogfight combat sequences. Battle your way through over 20 huge levels and six unique locations to defeat Cortex and save the world.

In a mysterious space station orbiting the Earth, Uka Uka is upset with Doctor Neo Cortex for failing him once again, but Cortex promises a plan that will bring the Earth's inhabitants down to size. Cortex then introduces his relatively new Planetary Minimizer, in which he immediately uses to shrink the Earth down to the size of a grapefruit. The situation is brought to Aku Aku's attention when Cortex taunts the now-microscopic people of Earth. When Aku Aku informs Crash of the Earth's predicament, Coco assumes that Cortex is using the Crystals to power up his shrinking machine, and requests that Crash must find the same kind of Crystals in various locations around the world, in which she will use to build a device that will reverse the effects of Cortex's Minimizer. After Crash manages to defeat Dingodile, Doctor N. Gin and Tiny Tiger, Cortex decides to deal with Crash himself by firing the Planetary Minimizer at him. Unfortunately for him, Crash tricks the doctor into shrinking the colored Gems that stabilize the Minimizer, causing it to malfunction. The unrestrained effects of the Minimizer fuse Cortex and his minions together, creating a monster known as Mega-Mix, who chases Crash down the space station's hallway in an attempt to kill him. Fortunately, Crash escapes back to the Earth, just in time for Coco to use the Crystals that he has gathered to return the Earth back to normal. The Earth is returned to its original size, while the space station outside Earth explodes with Cortex and the others in it.