The blitzball player Tidus lives in the hypermodern city of Zanarkand, enjoying a carefree life as star player of the blitzball team the Zanarkand Abes. His life soon turns upside down however when a gigantic monster called Sin destroys his entire city and casts him into an unknown world that differs greatly from what he is used to.

Washed up on a small island called Besaid, he quickly befriends the local blitzball captain, Wakka, and soon meets the summoner Yuna who has just obtained her first aeon and is preparing to leave on a pilgrimage across Spira with her guardians. As is tradition in the Yevon faith that resides in Spira, a summoner will take on a pilgrimage, travelling from temple to temple throughout Spira and gaining the ability to summon each Aeon that resides in the temples. The goal of this pilgrimage is to obtain the Final Aeon and use this to defeat Sin.

Since there are many fiends and obstacles on such a pilgrimage, a summoner will always be followed by one or more guardians, whose job are to protect the summoner at all cost. Tidus soon become Yuna's guardian, along with Wakka, a reserved, but caring black mage Lulu and the Ronso outcast Kimahri. Along the way, they will meet the mysterious and skilled warrior Auron and a cheerful young Al Bhed girl named Rikku. These two also join the group as guardians.

The story is about the pilgrimage, and how the group unfold the truth about Yevon and Sin. It is also a story about Tidus, and how he through his search for his homeland learns who he really is, and how his life is linked to Spira's Spiral of Death.