The unscripted reality show will be set in the Clerks director's New Jersey comic book store Secret Stash, according to The Hollywood Reporter.
"Draper. Meth. Zombies. This show couldn't be on a better network," said Smith in a statement, referring to the network's scripted series Mad Men, Breaking Bad and The Walking Dead.
"AMC is to television what Miramax was to cinema back when I first got in the game - they're the premier destination for any story-teller looking to spin an offbeat yarn that no other outlet has the stones to touch."
Smith will executive produce the series alongside Elyse Seiden, who worked with him on Red State, and Charlie Corwin's Original Media.
"The comic book store is, in many ways, the corner bar for comic book fans," said Joel Stillerman, AMC senior vice president of original programming, production and digital content.
"It is still this place where everybody knows your name, and you can go and geek out with like-minded people. If I lived closer, I'd want to hang out here."
Smith is a renowned comic book fan, having written on high-profile titles including Batman and Daredevil.