[3] The concept for the game originated from a 1992 demo video for the Amiga titled "Joe Pencil Trapped In The Comix Zone", animated by Peter Morawiec.

Sketch Turner, a "starving artist" and freelance rock musician living in New York City, is working on his newest comic book, Comix Zone.

It is the story of the New World Empire's attempt to defend Earth from an invasion of alien renegades, with inspiration coming from Sketch's oddly vivid dreams and nightmares.

In this instant, its main villain, a powerful mutant named Mortus, escapes the comic book's pages, desiring to kill Sketch so he can become flesh and blood and take over the real world.

Inside the comic book, Sketch meets General Alissa Cyan, who believes he is "the chosen one" who came to save their post-apocalyptic world from the evil of Mortus and the alien invaders.

Following this Alissa comes to the real world with Sketch and Roadkill and joins the army, eventually becoming Chief of Security for the United States.

Roadkill is given a vast amount of mozzarella cheese and spends a lot of time exploring the city's new sewer system when not sleeping under a pile of Sketch's dirty socks.

Comix Zone becomes an instant sensation, selling out on the first day, making Sketch famous as it becomes the best-selling comic book ever and the three live happily together, though a sequel hook in the end credits ominously implies that might change someday...[5] If the players take too long to defeat Mortus though the chamber will completely fill with liquid and Alissa will drown shortly before the nuke self-destructs.

[6] Comix Zone is an action platformer in which players control Sketch as he progresses through panels of his comic book, hoping to reach the end and escape before his own creations finish him off.

[7] The story was inspired by the 1985 music video for "Take On Me" by A-ha, which depicts a race car driver in a comic book connecting with a woman in the real world.

[10] Morawiec presented the video, "Joe Pencil Trapped in the Comix Zone", to STI head Roger Hector in December 1992.

[12] The initial protagonist was Joe Pencil, a "geeky-looking" character who Morawiec based on "the classic comic book angle of a scrawny kid getting transformed into a powerful superhero.

"[7] Sega's marketing department objected to the character's name and design, so he was renamed Sketch Turner and Morawiec, a fan of the Smashing Pumpkins, redesigned him to resemble a grunge rocker.

Morawiec did not want Sketch to be followed by a human or a large animal, so he conceived Roadkill since a rat "didn't take up a lot of screen space, and we could do quite a bit with it in terms of puzzles and such.

[11] DeZuniga designed the beginning and ending sequences; he drew the art with ink and pencils before scanning it into a computer and processing it for the Genesis.

[16] As development progressed, Stephens found it challenging to program the game so it would fit within two megabytes while being able to decompress large pages of graphics during play.

[17] When STI sent Comix Zone to Sega of Japan for review, it received a note claiming the game "embodied everything that was wrong with American culture".

[21] In retrospect, Morawiec felt the development would have greatly benefited from the contributions of STI's more experienced Japanese staff, who had split from the main team following the release of Sonic the Hedgehog 2 (1992).

[28][29] The port, released when Microsoft was promoting Windows 95 as a legitimate game platform, is largely identical to the Genesis version, though it features a MIDI rendition of the soundtrack.

[22] Sales of Comix Zone were hampered by its late release in the Genesis' lifecycle, after the worldwide launch of next-generation hardware like the Saturn and Sony's PlayStation.

[21] STI originally planned for the bundled CD to contain several Comix Zone tracks performed by a grunge band that Drossin had formed in Los Angeles, but Sega chose a different approach.

They also found problems with the controls: "Sketch can't move rapidly around the panel, and button slamming yields unpredictable results."

Its significantly smaller screen size that allows much less on-screen was said to reduce the effect of seeing into the other frames around the player, making it more like a traditional platform game.