Issues ranged between 40 and 64 pages in length, printed mostly in black-and-white with a color cover but occasionally including sections printed in one or two colors, notably a series of stories by Al Columbia.

A significant proportion of Zero Zero's pages were given over to serialized works, including Richard Sala's The Chuckling Whatsit, Dave Cooper's Crumple, Mack White's Homunculus, Kaz and Timothy Georgarakis's Meat Box, and Kim Deitch's The Strange Secret of Molly O'Dare and The Search for Smilin' Ed.

Derf Backderf's short strip "My Friend Dahmer", which he later expanded to an award-winning graphic novel of the same name, also appeared in its pages.

Early issues of Zero Zero were not numbered, but the back cover of each issue featured a captioned illustration depicting an ordinal "Sign of the Impending Apocalypse" which also served as an ad hoc numbering system.

For the twenty-seventh and final issue this feature was replaced with an Al Columbia strip, "Vladimir Nabokov's 'Cheapy the Guinea Pig'", depicting the killing of an experimental subject.