At the conclusion of the prequel, Fate/Zero, Saber was ordered to destroy the Holy Grail by her then-master, Kiritsugu Emiya via use of a Command Seal, but only succeeded in destroying its physical form and was thus summoned again by Shirō Emiya to fight in the Fifth War during the events of Fate/stay night. In both wars, her wish to the Grail is to redo her life so that a better person would take her place as king of Britain.
In the Fate route of Fate/stay night, Saber falls in love with Shirō, who then convinces Saber that she should accept her life for what it is rather than wishing to change her life. She then destroys the Holy Grail with Excalibur and is sent back to her original time, dying on the hill. During the events of Last Episode, this Saber reunites with Shirō after some time in Avalon.
In the Unlimited Blade Works route of Fate/stay night, Saber is stabbed by Caster's Rule Breaker, and temporarily becomes her unwilling Servant. After Caster is killed by Archer, Rin Tohsaka then forges a contract with her, becoming her new Master; however, despite being under Rin's command, she pledges her loyalty only to Shirō. She then destroys the Holy Grail with Excalibur. In the Good End of this scenario, she lives on in the world as Rin's familiar. In the True End, she disappears, similar to the Fate Scenario.
In the Heaven's Feel route, Saber is consumed by the Holy Grail during a battle with True Assassin and becomes a vastly stronger, corrupted version of her former self, Saber Alter, and a Servant under Sakura Matō. In the Normal End and True End, Saber Alter is defeated and killed by Shirō with the help of Rider. In the 'simple' end, Saber Alter is defeated by Shirō in one-on-one combat, at the cost of the latter's mind.
In the fandisc/sequel, Fate/hollow ataraxia, Saber continues to protect Shirō, though it seems their relationship has turned more towards Saber having the major control over the relationship with Shirō. She kills Archer when he attacks Shirō in one loop. In another loop, Saber is killed by Bazett's Fragrach when she tried to use Excalibur on Bazett. In the final loop of Fate/hollow ataraxia, Saber aids Shirō/Avenger in reaching the Grail by fending off the mysterious monsters (which were in fact leftover parts of Avenger wishing to continue the loop) with other Heroic Spirits.