The theme of Seventh Cross is evolution. The player begins with a protist, and through eating and consuming, progresses through two other stages until it becomes an animal. The game begins in a lagoon, where the player's organism must avoid predators while nourishing itself. If the creature dies, it is returned to its lowest form unless it has successfully evolved into its 'origin' stage, in which case the creature regresses to that instead. After death, any parts gained by evolution are kept, but any gathered food is lost.

Seventh Cross contains six stages, each with a boss. The stages take place in different biomes, ranging from the pond to a barren future.