Dr. Cortex found a evil mask in anicent temple and awaken it. The evil mask named "Uka Uka" has awaken and seek revenge on his brother, Aku Aku. They discover that they can go back in time and gather more villains.
- Crash Bandicoot:A genetically-advanced Eastern Barred Bandicoot who lives the life on N. Sanity Island and the main hero. He is a very emotional character who is quick to laugh and quick to cry. While he has a danger-loving, fearless nature and loves a good fight, he prefers relaxing in the sun and rarely seeks out trouble deliberately and has more of the Mind Over Mutants version.
- Aku Aku (voiced by Greg Eagles): He is an ancient spirit that lives within a mask and guides Crash, his sister Coco, and their friends as they defeat the forces of evil. In this film, learns that his evil brother has return and must stop of going back in time.
- Coco Bandicoot (voiced by Vitoria Justice): Crash's little sister. She is the highly intelligent and spirited younger sister of Crash Bandicoot. She often aids her big brother by building gadgets ideal for the situation or even tagging along with him in his journeys, using self-taught martial arts to defend herself.
- Crunch Bandicoot (voiced by Chris Williams):a genetically altered bandicoot who was originally created by Doctor Neo Cortex to destroy Crash Bandicoot. After his defeat to Crash, Crunch had a change of heart and now tries to be a positive role model to children. He has become Crash and Coco's friend and protects them from harm, living with them like a brother. He is a parody of Mr. T and talks like him.
- Tawna Bandicoot
- Dr. Neo Cortex
- Uka Uka (voiced by John DiMaggio): The evil brother of Aku Aku and works with Cortex to destory the forces of good.
- Nina Cortex (portrayed by Elizabeth Gillies): Dr. Cortex's niece and young evil genius that graduted from high school.
- Dr. Nitrus N.Brio: A fellow mad scientist with a potion that change him to a Hulk-version monster and works with Dr. Cortex for a long time returns to him and Uka Uka.
- Dr. N. Gin (voiced by Nolan North): An insane Cyborg lackey who stands in for giving assistance to Doctor Neo Cortex when he starts, replacing Doctor Nitrus Brio. He is bipolar, sado-masochistic and extremely madman, even showing low self-esteem and acts like his Crash of the Titan counterpart.
- N Tropy: A friend of Cortex and discovered a way time traveling, which starts out perfect until Crash and his frineds follwing them to time.
- The Cortex's experiments: They are created after the Bandicoot escaped and sent to destory them.
- Dingodile (voiced by Dee Bradely Baker): Half dingo and half crocodile, the third experiment to meet Crash and escape from the 1st film.
- Ripper Roo (voiced by Bumper Robinson): A blue kangaroo mixed with a psychopath DNA part from Cortex's insane side. He is a insane psychopathic, and somewhat dangerous, behavior. In this film, destoryed from laser blast with a "That's All Folks " sign.
- Tiny Tiger: (voiced by Chris William): a genetically-advanced upright cave sabertooth tiger that more smarter and portrays more like his Crash of the Titans counterpart, thanks to Crash.
- Komodo Brothers: Royal Komodos with DNA of Genghis Khan given by N.Brio and sent to destory Crash in the age of the Dinsaurs, named Joe and Moe. Joe is the skinny one with a lot of speed and able to spin for a long time until getting dizzy.Joe speaks with an accent similar to Kaa the Python from "The Jungle Book", that is, with long S, C or Sh syllables, such as "Let'sss Raccce" (but this doesn't necessarily always happen). Joe tends to give future blame towards a worthy opponents.
- The Twins: Twin pet birds that has telekenise and matter builder powers, created by Dr. Cortex and wear a alien space suit. They taken over the future time line and faces Carsh and Aku Aku.