From 1956 to 1957, he began to make comic books professionally for "Far West" or "Coeurs Vaillants" ("Brave Hearts".) It's at this time that he met Jean-Claude Mézières, future author of Valérian.

In 1958, he spent 16 months in Germany and 11 months in Algeria for his military service where he spent all his time drawing! It's in this period that he met Joseph Gillain, nicknamed Jijé, who played an important role in his graphic development and was also a real father for him. After returning from the army, he started making illustrations at the Hachette studio, for an encyclopedia about the history of civilization, along side of Mézières.

Then in 1962, he went to see Gillain who suggested he make a comic book for him.

In 1963, he drew "Fort Navajo", the first story of "Blueberry", in "Pilote" (J.M. Charlier's screenplay) and at the same time, he published short stories for Hara-Kiri, under the pseudonym Moebius.

In 1969, he made a series of science fiction illustrations for Opta.

In 1974, he drew "Cauchemar blanc" ("White Nightmare") for "l'Echo des Savanes", "le Bandard fou" ("The Crazy Gangman") at Fromage Publishing and "l'Homme est-il bon?" ("Is Man Good?") for "Pilote" : the "Moebius" style asserts itself completely.

In 1977, he worked on the costumes for Ridley Scott's "Alien".

In 1978, he made the storyboard of the "Maîtres du temps" ("Masters of Time") by René Laloux and illustrated "les Yeux du chat" ("Eyes of the Cat") a screenplay by Jodorowsky.

In 1980, for Walt Disney Production, he designed the storyboard for Tron and started on the adventures of John Difool, another screenplay by Jodorowsky.

In 1983, he created "Sur l'étoile" ("On The Star"), a publicity comic strip made for Citroën. This begins the Moebius superstar years.

In 1984, he moved Los Angeles. Claudine, his wife, set up the company Starwatchers Graphics, a company specialized in the publishing and distribution of products which are derived from comic books. Jean-Marc Lofficier (artistic agent and company manager) tried to make Giraud & Moebius known to the American public by convincing the people working for Marvel to publish certain pieces of work.

In 1985, he went to Tokyo and made the scenery and costumes for the animated film "Little Nemo" adapted from the comic book by Winsor McCay.

In 1989, he returned to Europe and started working on "A suivre". At Charlier's death, he took on the "Blueberry" series alone.

In 1992, he worked on Starwatcher, an ambitious French project because it was made entirely with computer-generated images (lack of funding caused the project to be abandoned).