Katsuhiro Ōtomo was born on April 14, 1954, in Tome, Miyagi Prefecture, Japan. Growing up in a rural area, he developed a deep interest in reading and drawing manga, citing Osamu Tezuka's Astro Boy and Mitsuteru Yokoyama's Tetsujin 28-go as early influences. After moving to Tokyo following high school, he began his professional career as a manga artist, publishing his first work, an adaptation of Prosper Mérimée's Mateo Falcone titled A Gun Report, in 1973.

Ōtomo first rose to prominence as a leading figure of the manga New Wave in the late 1970s, in part due to his unfinished 1979 series Fireball, which introduced a more cinematic and realistic style to the medium. His first major completed science-fiction work was Dōmu, serialized from 1980 to 1981. The story, a psychic thriller set in a decaying Tokyo apartment complex, won the Nihon SF Taisho Award and the Seiun Award for Best Comic, establishing his reputation for detailed artwork and sophisticated storytelling.

Ōtomo is best known as the creator of Akira, which began serialization in Kodansha's Young Magazine in 1982 and ran for eight years, totaling over 2000 pages. The epic post-apocalyptic narrative follows biker gang members in Neo-Tokyo who become entangled in a secret military project involving powerful psychic children. The manga was a landmark work that helped redefine the potential of the medium for international audiences. In 1988, he directed the landmark animated film adaptation of his own manga, condensing its sprawling narrative into a visually ground breaking feature that he storyboarded entirely by himself. The film was a massive success worldwide and was instrumental in popularizing Japanese anime in the West.

Beyond Akira, Ōtomo has consistently worked as an original creator across both manga and anime. He wrote the screenplay for the 1995 animated anthology film Memories, which was based on three of his own manga short stories. The segments include Magnetic Rose, based on his story Kanojo no Omoide; Stink Bomb, for which he wrote the script; and Cannon Fodder, which he both wrote and directed. He also wrote the script for the 1991 film Roujin Z. In 2001, he wrote the screenplay for the film Metropolis, an adaptation of Osamu Tezuka's manga of the same name. Ōtomo created the original story and picture book Hipira: The Little Vampire in 2002, which was illustrated by Shinji Kimura. His manga short story A Farewell to Weapons, originally published in 1981, was adapted into an anime segment for the 2013 anthology film Short Peace, for which he served as a director and producer on other segments, including Combustible.

Ōtomo's artistic identity is characterized by a highly detailed, realistic drawing style that marked a departure from the more stylized conventions of earlier manga. He sought to balance fantasy with realism, often using friends as models to achieve naturalistic character designs. His work is noted for its cinematic pacing, complex world-building, and meticulous architectural backgrounds, with the environment often serving as a central element of the narrative. Recurring themes in his work include post-apocalyptic settings, the abuse of power by military and governmental institutions, adolescent rebellion, and the dangerous potential of unchecked psychic or technological power. He has cited French cartoonist Moebius as a major influence on his artistic development.

Ōtomo's industry significance is immense. He is considered a pioneer who brought a new level of cinematic technique and gritty realism to manga, influencing generations of artists, including Naoki Urasawa and Satoshi Kon, who worked as an art assistant for Ōtomo early in his career. His directorial work on the Akira film set a new standard for animation production and remains a cultural touchstone. He has received numerous accolades for his contributions, including being decorated as a Chevalier and later promoted to Officier of the French Ordre des Arts et des Lettres, induction into the American Eisner Award Hall of Fame in 2012, and receiving Japan's Purple Medal of Honor in 2013. In 2015, he became the first manga artist to receive the Grand Prix de la ville d'Angoulême.