Destructo Box's humble beginnings stem from a dorm room at Indiana University. Co-creator Joey Reinisch worked for IU's student television network (IUSTV) at the time and had been kicking around animation ideas for a potential show. Working from personal and campus-owned equipment, Joey began creating promos for IUSTV with the design and sensibilities that would eventually become the familiar Destructo Box style. Co-creator Phil McLaughlin teamed up with Joey to flesh out more ideas for the show and assist in its production.
The earliest version of Destructo Box consisted of three skits in a ten minute format. The three skits would revolve around a single locality, on which the world would end at the end of every episode. The fourth and fifth episodes of "Season Zero," as it is colloquially referred to by the parties who witnessed and remember it's run, were each independantly close to full ten minute skits, making them the two longest single stories in the show's history, regardless of incarnation.
The intro sequence showed the creation of featureless characters in a cookie-cutter/factory fashion. These characters rolled off the assembly line into a cubical world and, lid closed, the planet was promptly flattened revealing the title of the show in blood spilling out of the box. The sequence featured the same Alex Clark theme briefly heard in the Newgrounds/Mondo Mini Shows incarnation of the show.
- "Treepet" - (written by Phil McLaughlin) Two anthropomorphic trees venture into a city to bring back a human as a pet for one of their sons. After removing a toothless, apple-loving bum from his "Bum Hose" they return with him to the forest where the bum meets an untimely end after urinating on another tree: the sapling's mother.
- "Rufus" - A homicidal dog hell-bent on keeping his owner's affection goes on a murderous spree against her would-be boyfriends.
- "The Philing Cabinet" - A pedophilic man disguised as local foliage tries to lure little Timmy and his friends into compromised positions.
- "Thus Spake Destructothustra"- (written by Aaron Waltke) Two astronauts are the world's last hope against a comet headed straight for the planet. Unfortunately for the world, one of them should never have made it through the space program and has a hankering for the starchy goodness only helmet-grown potatoes can provide. Fashioning a crude helmet from plastic wrap and venturing forth to plant a nuclear warhead on the comet, one of the astronauts loses his head and the world meets its end.
- "Ed gets E.D." - A poor man named Ed faces the realization that he is not satisfying his girlfriend and seeks medical help. After being put through a battery of tests to make his "dingleling go dingleling" it is revealed his doctor is a maniacal man, bent on destroying the producer of ED medication which had left him disfigured. His plot fails when his genitalia-shaped missile fails to launch.
The greatest assets of Joey and Phil's creation were the friendships they built within IU that lead to their characters having voices as well as assistance in editing, story ideas, script direction and sound effects. Animation was done primarily by Joey himself, while audio was parsed and recorded by both Joey and Phil.