Mayuzumi was a student of Tomojiro Ikenouchi at the Tokyo National University of Fine Arts and Music immediately following the Second World War, before going to Europe where he attended the Paris Conservatoire National Supérieur de Musique.
He was initially enthusiastic about avant-garde Western music, especially that of Varèse, but beginning in 1957 he turned to pan-Asianism for new sonorous material. Like the novelist Mishima Yukio, whose novel The Temple of the Golden Pavilion he set as an opera (Kinkakuji, 1976), Mayuzumi opposed the westernization of Japan and tried to emphasize his native cultural identity in his work.
A prolific composer for the cinema, he composed more than a hundred film scores between Waga ya wa tanoshi (It's Great to Be Young) in 1951 and Jo no mai in 1984. The best-known film with a score by Mayuzumi is probably The Bible: In the Beginning (1966). He also wrote many pieces for wind band that have been recorded by the Tokyo Kosei Wind Orchestra.
Mayuzumi was the recipient of a Suntory Music Award in 1996.