The character Space Ghost hosts a talk show, Space Ghost Coast to Coast, which began broadcasting in 1994 on Cartoon Network. Villains Zorak (a giant praying mantis / locust, depending on the particular show) and Moltar (a lava creature inside a metal suit) were Space Ghost's sidekicks (with guest appearances from many other old SG villains, most notably Brak). The show, as well as the short-lived Cartoon Planet, was a spoof of late-night shows such as David Letterman. Celebrities interviewed by Space Ghost included Beck, Jack Black, The Ramones, Metallica, and Jim Carrey.

The show relied heavily on absurd, surreal, or even dadaist humour. SGC2C continued to 2004 as the eldest program on Cartoon Network's late-night comedy/action programming block, Adult Swim. Space Ghost's name on SGC2C is revealed to be Thaddeus (Tad) Ghostal on the episode "Bobcat Goldthwait & The Ramones". The characters of Jan, Jace and Blip appeared twice on the show. The first was a brief appearance in the episode "Jerk" where they were trying to call in to the show and Space Ghost hangs up on them. Jan, Jace and Blip return to sue Space Ghost. They claim that Space Ghost exposed teenagers to interstellar gases, laser rays, and unearthly atmospheres that stunted their growth. They sue for back wages and damages stemming from emotional distress, mental cruelty, and for preventing them from attending school. The charges were dropped after their lawyer quit the case.

Coast to Coast in turn had its own spin-off starring Brak and Zorak called The Brak Show.

On the first parody series, Space Ghost was voiced by Gary Owens. On the later series, Space Ghost is voiced by George Lowe, who is also Dad on The Brak Show.

After approximately 7 seasons the show went into hiatus, and the writers Dave Willis and Matt Maiellaro used characters they developed in an unaired episode ("Baffler Meal") to create the popular "would-be spin-off" Aqua Teen Hunger Force. After that show proved successful, Baffler Meal was animated and aired in 2003.

Currently, new episodes of SGC2C appear on the "Animation" channel of the GameTap service. Guests seem to be either gaming celebrities or non-mainstream musicians.