Created by album and book cover designer Dean Motter, Mister X was developed for a year in close collaboration with comic artist and illustrator Paul Rivoche, whose series of poster illustrations stirred up great interest in the project. The series published early work by comic artists who would later emerge as important alternative cartoonists, including Jaime Hernandez, Gilbert Hernandez, Mario Hernandez, Seth, Shane Oakley and D’Israeli.
A highly successful promotional campaign with posters and ads followed for the next year, while Motter and Rivoche struggled to produce an actual issue of Mister X. When Rivoche quit, Vortex Comics president Bill Marks became more skeptical than ever that Motter would be able to produce the series on time, and decided to turn the work over to the Hernandez brothers. The first four issues were written and illustrated by Jaime and Gilbert Hernandez, with additional writing by Mario Hernandez. The Hernandez brothers quit over payment delays from Vortex. Issues 5 through 14 of the series were then written by Motter, with issues 6 through 13 illustrated by Seth.