As a summoner, Yuna travels across Spira to end the threat the malevolent force Sin poses to her world, aided by her aeons, and even more so by her guardians, whose duty it is to protect her along her journey. Yuna begins her pilgrimage across Spira with three guardians: Kimahri Ronso, who took care of her after she was orphaned; Lulu, who treats her as a younger sister; and Wakka, with whom — along with Lulu — she has been close friends since childhood. After Tidus arrives in Besaid, she takes him as her fourth guardian, and later, Auron — who was also guardian to her father — becomes her fifth. Finally, Yuna's maternal cousin Rikku becomes Yuna's sixth and final guardian shortly after Tidus and Wakka thwart her attempt to kidnap Yuna with an underwater machina. During the course of the game, Yuna is forced to grow in character. She becomes battle-hardened and her Yevonite beliefs are shaken and eventually shattered. Furthermore, her ever-growing relationship with Tidus causes her to question her quest, and think more for herself. This is evident when she is composing the video sphere she intends for her friends and guardians to view after her death- she confesses that the thought of not being with Tidus scares her.
As she learns more about Sin — against whom she has trained in the summoners' arts to use the Final Summoning — Yuna becomes caught up in the plot of Maester Seymour Guado, who claims to want to unite Spira by marrying her, but who seeks to use her to become the next Sin and destroy Spira. Yuna had planned to marry him in exchange for him turning himself over to Yevon's judgement- the plan fails and Yuna and her guardians, recently informed of Seymour's crime, fight and kill him. She is later kidnapped and brought to Bevelle, where her guardians launch a rescue attempt that ends in their capture. When she discovers that the Church of Yevon uses machina, violating its own teachings, and that it has no intentions of allowing her to send Seymour despite his evil, her faith in Yevon is shattered. When Tidus eventually learns the full implication of the Final Summoning — that Yuna will sacrifice herself, as her father did, in order to bring about a temporary period free of Sin (called "the Calm") — his perspective persuades her that they can find another, more permanent way to rid Spira of the threat of Sin. Tidus and Yuna's mutual love for one another intensifies as the party approaches its destination. In the romantic setting of a sphere pool, Tidus shares memories of his native Zanarkand and toys with the idea of showing Yuna his home (even though it is becoming clear that he can never return). Yuna realizes she will never live to see it, and the burden she has been carrying in silence for so long finally causes her to break down, and she starts crying uncontrollably. Tidus moves to comfort her, and in their despair they kiss. In the morning, Yuna has little choice but to proceed with her pilgrimage. But when the quest draws to a close, Yuna is shocked to discover she must sacrifice one of her guardians to provide the soul for the Final Aeon, and that as the Final Aeon will become Sin, the Final Summoning can never defeat it. With Tidus's encouragement, she decides to break Yevon's endless cycle and find another way to defeat Sin, one which will not provide it with the means to rise again. This eventually leads to a confrontation with Sin and the true progenitor of Spira's sorrows, Yu Yevon. Yuna's group defeats Braska's Final Aeon, whose fayth is Tidus's father Jecht, and after defeating Yuna's aeons as Yu Yevon possesses them, defeats Yu Yevon himself. However, as a consequence of defeating Yu Yevon and ridding the world of Sin, Tidus broke Yu Yevon's hold on the fayth, resulting in Tidus vanishing into nothingness as the fayth wake up. Before he leaves for the Farplane, Yuna tells him she loves him (in the Japanese version of the game, she says "Thank you" instead, basically thanking Tidus for protecting, supporting, and loving her). In Final Fantasy X International, an extra scene called "Eternal Calm" recounts Yuna's thoughts two years later as she tries to return to her normal life back in Besaid. Being the high summoner who permanently defeated Sin, she has constantly been plagued by visitors and tourists ever since, and more than once has even been asked by the elders of her town that she should be considering marriage and settling down. As Yuna contemplates the changing Spira and her role in it, Rikku comes to visit, and shows her a sphere Kimhari found that she believes shows Tidus. Feeling that she deserves an adventure of her own, Yuna literally ran off with her cousin without a word, fuelled by hope that she may know more regarding Tidus.