The story of Chrono Cross revolves around the character Serge, the protagonist, who, as a small child, is supposed to drown, but is saved by a powerful force. The resulting shift in the world's history creates two distinct parallel dimensions. In one dimension, he survives and lives for 10 years before the game begins. In the alternate dimensions, he drowns in a beach near his home.

The plot itself revolves around Serge's unknowing efforts to free Schala from the Time Devourer: a fusion of Lavos, the ultimate enemy from Chrono Trigger with the capacity to destroy the planet, and Schala, a princess of Zeal and sister of Magus with immense magical power who has disappeared into the Darkness Beyond Time due to an accident. Years in the future, Belthasar, a former guru of Zeal, discovered that the Time Devourer had formed and planned to consume all spacetime; he thus set in motion an almost ludicrously complex chain of events meant to give rise to and guide Serge to venture to the Time Devourer and use an artifact known as the Chrono Cross to restore the dimensions to one and free Schala from Lavos's grasp. While the plot is sound, its delivery is criticized by some as excessively complex. Unlike Chrono Trigger, in which the basic plot is simple and straight-forward, much of the dialogue throughout the game of Chrono Cross must be read carefully in order to make sense of the story. Because some Chrono Cross players do not listen to much of the game's characters, they mistakenly accuse the plot of being weak and senseless. Thus, many players resort to guides, such as the following link, to understand the story's intricacies.

While Chrono Cross incorporates elements from Radical Dreamers, the stories of the two games are incompatible. To resolve the scenario continuity issue and to acknowledge the existence of Radical Dreamers, the designers suggested that the events of Radical Dreamers did happen, but took place in a parallel dimension. This can be found by reading one of the computer consoles in Chronopolis, a city which was pulled back in time due to a failed experiment. Chronopolis now monitors the El Nido Archipelago, in an attempt to prevent a paradox from occurring which would prevent its existence in the future. The most notable difference is that Magus is absent from the game. While confirmed to be Magil in Radical Dreamers by both the game and its creator, Magus does not assume the identity Guile in Chrono Cross, as is commonly assumed. It was noted in an interview that the developers originally planned for Magus to be in the game, but scrapped the idea due to difficulties representing his story amongst forty-three other characters.