Before any part of the episodes were written, the guests were interviewed by a crew member, sometimes wearing the Space Ghost costume made famous by Andy Merrill in some Cartoon Planet (1997) intros. The interviewer also instructed the guest to address him as "Space Ghost" to maintain continuity. After an interview was done, the writing crew went back over it, taking pieces out of context and out of order, assembling them into the responses to Space Ghost and the rest of the cast. Most of the show's earlier guests assumed they were participating in a relatively straightforward interview. As the series became more popular, however, more and more guests became at least peripherally familiar with what was going on.
In the show's early stages of production, Hervé Villechaize was set to be Space Ghost's sidekick, but these plans were halted when the actor tragically committed suicide.
Originally created as a Cartoon Network promo. The programmers had been using old cartoon shows and re-engineering them to act as hosts for a day. Each classic cartoon had its own gimmick; Space Ghost's segment was made a late night talk show and, for rhyme's sake, was called "Space Ghost Coast to Coast".
Space Ghost interviewed Tommy Wiseau in a series of bumpers for Adult Swim's April Fools' Day 2010 showing of The Room (2003).
The DVDs for the show have run into problems because some of the interviews weren't licensed for home video.