The band was formed in Akron, Ohio, in late 1981 by Tom Seiler of local punk group The Bursting Brains, Mick Hurray of the neo-surf group The Nelsons, and Jim Friend of V-Nervz.
The band went through a few bass players before placing an ad in the Cleveland free paper Scene.Brad Warner, who had been in a new wave group called Mmaxx, answered the ad and after an afternoon audition he was accepted into the band. Warner remained a member of the group until its dissolution.
In December 2005, Jim Lanza hatched the idea of reviving a handful of old Cleveland-area punk bands for a one time show entitled Cleveland's Screaming. Warner decided to take the opportunity to create a documentary about the punk rock scene in Akron and Cleveland in the 1980s also entitled Cleveland's Screaming. The documentary was released in 2007.
Since they reformed, the band has begun writing and recording new music. In early 2013, the band signed to the record label Revolution Harmony. Zero Defex still plays shows as often as the band members are able.