After working as a bookkeeper for a while, Michele Pepe made a discrete debut in the comics field in 1976. His first comics where short stories about war, published in Super Éroica. A year later, he joined the Staff di If team, where he illustrated 'Fury', an animal series inspired by the American television series. While making drawings for Corrier Boy, Pepe illustrated sentimental stories for Il Monello and Intrepido. Afterwards, he cooperated on 'Gli Eroi del Mare', a series for Mursiavela publishers. In 1981 he had a brief appearance on the English market, with 'Sword of Justice' for the London-based Grandreams publishers.
In the early 1980s, Pepe drew the adventures of private-investigator Master in Adamo, followed by several comics for Lanciostory and Skorpio. At the same time, he became one the artistic directors of Bonelli publishers. He is also the illustrator of nine episodes of 'Zagor', two episodes of 'Martin Mystère' and an episode of 'Mister No'.