Following their defeat at the hands of Crash, Uka Uka attempts to liberate himself and Doctors Neo Cortex and Nefarious Tropy from their prison in the past. His latest effort rips open a hole in the fabric of space and time, and causes him to pass out. Cortex and N. Tropy swiftly escape, abandoning Uka Uka. They discover that the rift links their universe to the rest of the multiverse, and decide to make use of it to conquer all dimensions.
The game's levels take place and progress along a linear map that is divided into ten "Dimensions", each with their own theme. From this map, the player can switch between controlling Crash or Coco at any time. The game can be played in two different styles, which can be selected before the start of a new game and can be switched at any time in the options menu. The default play style is "Modern", in which the player will always return to the latest checkpoint when the player character dies. In the other play style, "Retro", the player is given a limited number of lives (represented by a floating head of the character currently in play), of which more can be collected within the levels. If the player's last life is lost, the level will be restarted from the beginning. Neither the game's difficulty nor reward progress is affected by the differing play styles.