Mamoru Nagano was born on January 21, 1960 in Maizuru, Kyoto Prefecture. He initially pursued fashion design at Takushoku University before leaving to work in the anime industry. His professional career began in 1983 when he joined the animation studio Sunrise, a move that followed his reception of the second SF Art Grand Prize in 1982. He made his debut in 1984 working under director Yoshiyuki Tomino on the television series Heavy Metal L-Gaim, where he was responsible for both character and mechanical designs. His work on L-Gaim introduced mecha designs featuring armor plates that appeared to fit loosely over an internal skeleton, a detailed and plausible approach that influenced a new wave of design in mecha anime. He also contributed mechanical designs to Mobile Suit Zeta Gundam, with notable creations including the Rick Dias and the Hyaku Shiki.

Nagano is the original creator of the long-running manga series The Five Star Stories, which began serialization in 1986 and continues to be produced. He also wrote and illustrated his first manga, Fool for the City, in 1985. To publish much of his work, he founded the company Toys Press, Inc. Beyond manga and anime, he has worked as a musician and fashion designer, and has been credited as a co-author and illustrator for the two-volume novel Schell Bullet alongside Kunihiko Ikuhara.

His work as an original creator extends to the anime film Hana no Utame Gothicmade. For this project, Nagano worked with the studio Automatic Flowers and took on multiple key creative roles, including producer, director, chief writer, and character and mechanical designer. The film was announced in 2006 and released in Japanese theaters in November 2012. Nagano is known for his elegant and graceful mecha designs, which often feature elongated lines, delicate curves, and a high degree of decoration and detail. This distinctive aesthetic, which he has described as being inspired by the look of dressed-up young women, has made him an innovator in the field. He is married to voice actress Maria Kawamura.