Gilles Mezzomo worked with the French National Railways before beginning his career in comics. He showed his work at the editorial offices of the magazine Spirou in 1991, and was assigned to take over the series 'Le Roi Vert' after the death of Jacques Armand. Mezzomo made four albums of this comic adaptation of Paul-Loup Sulitzer's novel together with the scenario-writer Annestay and later Denis Lapière between 1993 and 1995.
After 'Le Roi Vert', Mezzomo and Lapière started their series about the young sociologist 'Luka' at the publishing house Dupuis in 1995. Between 2004 and 2010, he made the western series 'Ethan Ringler, Agent Fédéral' together with scriptwriter Denis-Pierre Filippi. Mezzomo and Filippi continued their collaboration at Dargaud with 'Nouveau Monde'. Gilles Mezzomo also drew the 6th installment in Frank Giroud's 'Destins' series.