Cerebus has since its inception been self-published by Sim under his Aardvark-Vanaheim, Inc. banner. Sim's position as a pioneer self-publisher in comics inspired numerous writer/artists after him, most notably Jeff Smith (Bone), Terry Moore (Strangers In Paradise), and Martin Wagner (Hepcats).

The title character is a misanthropic three-foot tall bipedal gray aardvark ("We're all funny animals in a world of humans," says Sim) who has, at various points in his life, been a mercenary, Prime Minister of the fictional city-state of Iest, Pope (in the mammoth Church and State saga), and renegade. He is an extremely morally ambiguous character, at times sympathetic, at others almost unpalatably callous.

Inspired in some ways by the Steve Gerber character Howard the Duck, the earliest issues of Cerebus took the form of a parody of Conan the Barbarian and its genre. (Howard had even appeared on the cover of the first issue of his own comic as a parodic barbarian character.) The series developed artistic sophistication and originality very quickly. Citing as his self-originated commandment, "Thou shall break every law in the book", Sim has done everything from flipping the page from horizontal to vertical and all stages in between to alternating comics with prose narrative, to including real dead or living people (himself included) in the storyline, all in an effort to explode the conventions of the North American comic book in almost every conceivable way.

In 1979, Sim, who was at the time a frequent marijuana user, experimented with LSD, taking the drug with such impunity that he was eventually hospitalized. It was this incident that Sim claims led to the inspiration to produce Cerebus for 300 monthly issues. The episodic adventures strayed further and further from heroic fantasy, and the twenty five-issue graphic novel High Society segued the narrative into a complex political satire and drama. Sim was joined by Gerhard, who gave the series impressively rendered backgrounds that became a visual hallmark, after issue #65.

When Sim published the first Cerebus "phone book", a paperback collection of the High Society graphic novel, he angered retailers by offering the first printing via mail order only. The decision was a financial windfall for Sim, however, racking up over $150,000 in sales. Not long after, Sim became known for traveling to conventions and store signings in limousines (he spent $25,000 in limo service during his 1992 signing tour), and renting lavish suites at conventions at which he'd throw huge parties.

In the 1990s, Sim became an outspoken advocate of creators' rights in comics, and used the editorial pages of Cerebus to promote self-publishing and greater artist activism. Sim was also the biggest individual supporter of the Comic Book Legal Defense Fund; when he guest-wrote the 10th issue of Todd McFarlane's best-selling Spawn, Sim donated his entire fee — over $100,000 — to the fund.

It is generally agreed that the graphic novel Jaka's Story, a tragic character study dealing with gender roles and the political suppression of art, is perhaps the series' pinnacle of narrative achievement. However, later issues of the series became almost inaccessibly personal and began to alienate many long-time fans, his female readers especially — though their visual innovation remained unparalleled. Issue #186 contained a lengthy prose section of the narrative that was roundly attacked by both readers and critics for its overt misogyny. This was followed by an even harsher essay in issue #265 called "Tangents," in which Sim claimed there is a "feminist/homosexualist axis" engaged in a conspiracy to oppress men. He also argues, in all seriousness, that husbands should have the legal right to spank their wives and states outright that women are inferior to men.

Sim himself has appeared as a character in Cerebus, most notably to berate his creation in the graphic novel Minds. A writer entering his own fictional universe is not an idea which Sim can claim to have invented (see Kurt Vonnegut's Breakfast of Champions, Paul Auster's New York Trilogy and Grant Morrison's comic Animal Man), although he claims to have planned the encounter as early as 1979 — more than a decade before it actually took place.

Sim's behavior has become encreasingly erratic as the series nears its finale, and he has developed a reputation as a curmudgeonly eccentric - which many observers feel could taint his artistic accomplishment in completing Cerebus. He has reportedly cut all ties with his family and virtually all of his industry colleagues apart from Gerhard. He has had very public fallings-out with both Moore and Smith, the latter of whom Sim challenged to a fistfight in an editorial published in the comic. Smith, Sim claimed, lied about an argument the two had had over the infamous essay in issue #186. Sim also developed an adversarial relationship with Gary Groth, the confrontational publisher of The Comics Journal, an independently published comics magazine known for punishing criticisms and a decidedly non-mainstream editorial slant.

Sim has stated (in an editorial contained in issue #297) that he regards the production of Cerebus as of secondary importance to his religious practice. A 2003 magazine interview describes Sim as reciting a prayer of his own devising five times a day, and having sold much of his furniture to donate the money to charity as an act of religious asceticism.

Sim, once a very public figure in the comics industry, now rarely leaves his native Kitchener, Ontario home. The impending publication in March 2004 of issue #300 was met with a muted, rather than celebratory, response from the comics industry. In late 2001, Sim confirmed his plans following the completion of Cerebus were to take a long rest. He has dismissed concerns raised by some fans and former associates that he may commit suicide.

List of Cerebus collections to date