After a 3-installment trial run as an insert feature in Penthouse Magazine, Penthouse Comix was expanded into a standalone magazine. The first issue, a 96-page, color, magazine, appeared in spring 1994. It featured work by Adam Hughes, Garry Leach, Kevin Nowlan, Mike Harris, Arthur Suydam, Jordan Raskin, Horacio Altuna, and Milo Manara. Subsequent issues contained work by artists including Richard Corben, Tony Salmons, Bart Sears and Gray Morrow.
Two additional titles were later added to the line: The seven-issue Men's Adventure Comix (cover-titled Penthouse Men's Adventure Comix) (April/May 1995 - April/May 1996), and the three-issue (March/April 1995 - Oct./Nov. 1995) Omni Comix, the latter a companion to the science magazine Omni Magazine.
Editor-in-Chief George Caragonne was prone to erratic behavior and eventually purged Managing Editor Weisfeld, who had begun the stand alone magazine with Caragonne. Thereafter, artwork and money began to disappear from the Penthouse Comix office, top line artists abandoned the project, and overall quality and sales declined. Caragonne was eventually accused of embezzlement by Penthouse, fired and committed suicide in the summer of 1995. General Media then seized control of its comics-related publishing from the deceased Caragonne's packaging company and installed Dave Elliott as editor. The Penthouse Comix line was whittled to one magazine. Elliott edited the remainder of the magazine's run. General Media went bankrupt a short time later.