Druillet was born June 28th, 1944 in Toulouse, Haute-Garonne, France but spent his youth in Spain, returning to France in 1952 after the death of his father. A science fiction and comics fan, Philippe worked as a photographer after graduating from high school, drawing only for his own pleasure.
His first book appeared in 1966, entitled Le Mystère des abîmes (The Mystery of the Abyss). It introduced his recurring hero Lone Sloane and played on science-fiction themes partially inspired by his favorite writers, H. P. Lovecraft and A.E. van Vogt. Later, Druillet created book covers for republications of Lovecraft's work, as well as numerous movie posters.
After Druillet became a regular contributor to the Franco-Belgian comics magazine Pilote in 1970, his Lone Sloane saga grew steadily more flamboyant, as he pursued innovations including bold page designs and computer-generated images. His backdrops of gigantic structures inspired by Art Nouveau, Indian temples and Gothic cathedrals earned him the nickname of 'space architect'. Six tales about Sloane's exploits were collected in Les six voyages de Lone Sloane in 1972, hailed by many as his masterpiece, and Sloane was again the hero of the graphic novel Délirius (1973), written by Jacques Lob. In 1973, Druillet also produced the Moorcock's Elric-inspired Yragaël for Pilote, and Vuzz for the magazine Phénix.
In 1975 Druillet joined Jean-Pierre Dionnet, Bernard Farkas and Moebius to form the publishing house Les Humanoïdes Associés, and the magazine Métal Hurlant. This was to be a vehicle for his finest stories, and showcased a steady evolution in his graphical skills. His series Lone Sloane and Vuzz continued, and other stories of this period include La Nuit, and Nosferatu. In 1980 Druillet produced Salammbô, a comic-book trilogy based upon Flaubert's proto-heroic fantasy novel Salammbô.
Outside his work as a cartoonist and illustrator, Druillet has also been active in architecture, rock opera, painting, sculpture and digital art. He worked as a designer on the film, Sorcerer, directed by William Friedkin in 1976. He collaborated on Rolf Liebermann's Wagner Space Opera in the Opera de Paris in the late 70s to early 80s, and founded the Space Art Création in 1984. More recently he created the artwork and designed large parts of the background of the 2005 TV miniseries remake Les Rois maudits.