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Isayama was born on August 29, 1986 in Ōyama, Ōita, Japan. After graduating Ōita Prefectural Hitarinkou High School, he matriculated in the cartoon design program of the cartoon arts department, Kyushu Designer Gakuin. After graduating, he moved to Tokyo and started drawing his manga works.
In 2006, he applied for the Magazine Grand Prix known as MGP promoted by Kodansha Ltd. and his work "Attack on Titan" (Shingeki no Kyojin) was given the "Fine Work" award. Originally, he offered his work to the Weekly Shōnen Jump department at Shueisha, where he was advised to modify his style and story to be more suitable for Weekly Shōnen Jump. He declined and instead, decided to take it to the Weekly Shōnen Magazine department at Kodansha Ltd.
In 2008, he applied for the 80th Weekly Shōnen Magazine Freshman Manga Award, where his work "Heart Break One" was given the Special Encouragement Award.
His other work "orz" was chosen as a selected work in the 81st Weekly Shōnen Magazine Freshman Manga Award.
In 2009, his first serial work Attack on Titan appeared in Bessatsu Shōnen Magazine, a monthly magazine.
In 2011, Attack on Titan was awarded the 35th Kodansha Manga Award in the Shōnen category.