Guy is the son of Might Duy, who was known throughout Konoha as the "Eternal Genin". Duy was not bothered by this moniker and instead was grateful that other people cared enough to know him at all. Duy encouraged this same kind of optimism in Guy, as well as his belief that one always has youth and that they could both become taijutsu masters through diligent training. Guy did his best to embody his father's teachings, but had doubts that Duy's words were devoid of meaning. He nevertheless loved his father and fought others when they called Duy the "Eternal Genin" mockingly; when one of these fights landed him in the Konoha Hospital, Duy encouraged Guy not to be upset by this loss and to instead remember that victory is achieved by defending things that are important.
Guy applied to enter Konoha's Ninja Academy, but did not pass the entrance exam. Kakashi Hatake was not surprised due to Guy's lack of talent in ninjutsu and genjutsu, which Guy chose to take as a supportive observation. This strength of character convinced Kakashi's father, Sakumo, that Guy was not handicapped by his shortcomings and that he might be offered a position as an alternate in the year's Academy class. Guy was indeed allowed to enter the Academy with Kakashi, and upon graduation he was added to a team that, in the anime, was led by Chōza Akimichi. The team at one point entered Konoha's Chūnin Exams and passed to the final stage; Guy himself advanced to the exams' last one-on-one match, where he lost to Kakashi. While on a mission during the Third Shinobi World War, Guy and his team were attacked by the Seven Swordsmen of Kirigakure. They were rescued by Duy, who used the Eight Gates Released Formation to fight off the Seven Swordsmen. Duy died from opening all Eight Gates, but it satisfied his one rule for its use: giving his life to protect something precious, namely Guy.
Guy at some point decided that Kakashi was his lifelong rival, driven by a desire to prove his perseverance could be just as good as Kakashi's natural genius. He would constantly challenge Kakashi to contests of skill, from eating contests to Rock, Paper, Scissors. Kakashi was indifferent to these contests, which only fueled Guy's desire to defeat him. In the anime, Kakashi prevailed in the earlier of these competitions, but Guy soon started catching up, eventually achieving only a one point difference in their scores that has remained consistent over the years. Guy is proud of his score despite the fact that, because of how varied the contests are, it is hardly representative of anything. Through their competition, Kakashi and Guy became good friends; they were hanging out together on the night of the Nine-Tailed Demon Fox's Attack, yet were prevented from helping defend the village, instead being confined within a barrier to keep them safe.
In the anime, Guy was aware of the losses Kakashi experienced during and after the Third Shinobi World War and tried to help him deal with them. Following the death of Obito Uchiha, Guy filled in for Obito while Team Minato was on a mission into Iwa-territory. When they were surrounded, Guy tried giving his life to allow Kakashi to escape, but they were able to fight off their enemies until reinforcements arrived. Following the death of Rin Nohara, Kakashi's teacher, the Fourth Hokage, sent Guy to tail Kakashi on a mission in case memories of Rin started to get to him. This proved wise: when Kakashi began hyperventilating from using the Chidori - the same jutsu that killed Rin - Guy intervened in time to save Kakashi and take him home. Following the Fourth's death during the Nine-Tails' attack, Guy requested to be admitted into the Anbu so that he could help Kakashi through his growing depression. The Third Hokage refused his request, which Danzō Shimura seconded, explaining that Guy lacked the necessary darkness for Anbu-service. Guy witnessed this "darkness" when Kakashi provided backup for him during a meeting with the Land of Woods, wherein Kakashi mercilessly killed all the Land of Woods' forces. Guy asked the Third Hokage to remove Kakashi from the Anbu because these kind of acts didn't become him. When the Third eventually complied, Guy suggested that Kakashi try leading a team of genin to help him regain his lost kindness.
Guy at some point heard about a boy in the Academy who was unable to use ninjutsu or genjutsu. Guy approached this boy, Rock Lee, and encouraged him to use his youth to keep training. Lee was eventually added to Guy's Team Guy, along with Neji Hyūga and Tenten; in the anime, before accepting them, he required them all to demonstrate a desire to succeed no matter the odds. Guy took a particular interest in Lee after the team's first meeting, as Lee wished to become a splendid ninja who could only use taijutsu. Guy decided to dedicate his life to helping Lee achieve his dream, teaching him all he knew of taijutsu, telling him the same keys to self-improvement his father had taught him, and encouraging him to use a rivalry with Neji to push him to new heights. Lee developed well under his guidance, as did Neji and Tenten, though Guy felt it was best to have them wait a year before entering the Chūnin Exams.