Uryuu was primarily raised by his father, Ryuken, and grandfather, Soken, the latter of who taught and trained his grandson in the ways of the Quincy. Ryuken (who's profession was a clinic doctor) disapproved of Quincy training claiming that it wasn't worth the time because it didn't make any money. As a result Uryuu's relationship with his father has always been uneasy and strained at best. While Uryuu was still very young his grandfather was attacked and killed by a group of hollows while the poor boy could only watch. This event lead to his hatred of the Shinigami, who failed to come to his grandfather's rescue even though it is their job to dispose of dangerous hollows.
When Uryuu enters high school he discovers the existence of a Shinigami (one Ichigo Kurosaki) and confronts him, challenging him to a contest to see who can kill more hollows. It was Uryuu's hope that he would win the challenge and therefore prove that the Quincy's way of taking care of hollows was better. However the plan backfires when a menos grande (uber hollow) shows up and forces Uryuu and Ichigo to work together, also causing Uryuu to gain somewhat of a kind of respect for Ichigo.
Uryuu attempted to defend Rukia Kuchiki from being taken back to Soul Society but failed, causing him to send himself into a week's worth of training in order to master the Sanrei glove. He joins Ichigo and the others as a part of the rescue team that breaks into Soul Society in order to rescue Rukia from execution. While there he faces Mayuri Kurotsuchi, a shinigami and Captain of the 12 th Division. Kurotsuchi reveals that he was the one who ordered the Shinigami not to rescue Uryuu's grandfather from the hollow attack. It is also during this battle the Uryuu uses the Sanrei glove to temporarily increase his Quincy powers, but after the battle is over it also causes him to loose said powers indefinitely. He is then taken prisoner by Kaname Tosen, where he is reunited with the rest of the rescue team and later escapes with them. Once Rukia was saved Uryuu and the rescue team return to the human world.
After a brief time of little activity, arrancar begin to take interest in Uryuu's home town (mostly because of Ichigo). He is attacked by two incomplete arranar and although his efforts are valiant he is unable to defend himself. He is rescued, surprising by his father. Ryuken, seeing his son's weakness and being disappointed, offers to help his son restore his Quincy powers on the condition that Uryuu cuts all ties he has with shinigami. Uryuu agrees and his powers are restored after his new training is done.
After hearing that Orihime (a part of the rescue team, and his classmate) was kidnapped by the arrancar Uryuu once again joins Ichigo and what remains of the old rescue team to save her. Once they arrive in Hueco Mundo the group splits up in order to cover more ground and find Orihime quickly. Once he defeats Cirucci Thunderwitch almost single handedly he meets up with Abarai Renji who is about to be killed by the 8 th Espada, Szayel Aporro Granz. They were in the middle of this battle with the Espada when Uryuu was knocked unconscious and woke up in Econtra.