McCloud created the light-hearted science fiction/superherocomic book series Zot! in 1984, in part as a reaction to the increasingly grim direction that superhero comics were taking in the 1980s.
His other print comics include Destroy!! (a deliberately over-the-top, over-sized single-issue comic book, intended as a parody of formulaic superhero fights), the graphic novelThe New Adventures of Abraham Lincoln (done with a mixture of computer-generated and manually drawn digital images), 12 issues writing DC Comics' Superman Adventures, and the three-issue limited series Superman: Strength.
He is best known as a comics theorist or as some say, the "Aristotle of comics", following the publication in 1993 of Understanding Comics, a wide-ranging exploration of the definition, history, vocabulary, and methods of the medium of comics, itself in comics form. He followed in 2000 with Reinventing Comics (also in comics form), in which he outlined twelve "revolutions" that he argued would be keys to the growth and success of comics as a popular and creative medium. Finally, in 2006, he released Making Comics. Following publication, he went on a tour with his family that included all 50 U.S. states and parts of Europe.
He was one of the earliest vocal supporters of micropayments. He was also an adviser to BitPass, a company that provided an online micropayment system, which he helped launch with the publication of The Right Number, an online graphic novella priced at US$0.25 for each chapter. McCloud maintains an active online presence on his web site where he publishes many of his ongoing experiments with comics produced specifically for the web. Among the techniques he explores is the "infinite canvas" permitted by a web browser, allowing panels to be spatially arranged in ways not possible in the finite, two-dimensional, paged format of a physical book.
He created a comic book that formed the press release introducing Google's web browser, Google Chrome, which was published on September 1, 2008.
McCloud was the principal author of the Creator's Bill of Rights, a 1988 document with the stated aim of protecting the rights of comic book creators and help aid against the exploitation of comic artists and writers by corporate work-for-hire practices. The group that adopted the Bill also included artists Kevin Eastman, Dave Sim, and Stephen R. Bissette. The Bill included twelve rights such as "The right to full ownership of what we fully create," and "The right to prompt payment of a fair and equitable share of profits derived from all of our creative work."
Although McCloud sketches his layouts in pencil, the remainder of his work is done digitally, explaining in his 2006 book Making Comics that he had not used traditional materials like Bristol board, pens or brushes in years. After sketching layouts, which he says are "pretty tight", and include the full script, he scans them into an 18-inch computer tablet/monitor to use them as a guide for lettering them in Adobe Illustrator. After completing the lettering, he exports the files to Photoshop, where he fully renders the art at a resolution of 1,200 dpi, creating between five and fifty layers of finished art before flattening it into a single black and white bitmap, plus a greyscale page, if needed.