He is the co-creator and writer of the cult animated Adult Swim shows, Aqua Teen Hunger Force, Perfect Hair Forever, and the creator of 12 oz.

Maiellaro provides the voice of Err the Mooninite,[4] the Cybernetic Ghost of Christmas Past from the Future, and other various roles on Aqua Teen Hunger Force, as well as various characters for the other Adult Swim shows he's involved with.

An Aqua Teen Hunger Force episode entitled "Boston" was produced to serve as the creator's response to the incident, but Turner Broadcasting and Cartoon Network executives canceled it to avoid further trouble.

[7] Around 1999, Maiellaro and longtime friend Barry Mills formed the rock band Donnell Hubbard,[8] whose music was later used in a few episodes of Sealab 2021 (notably the song "Fishin' Hole").

In the opening credits of Aqua Teen Hunger Force, graffiti can be seen that reads "Donnell Hubbard is a dead man".

Maiellaro directed the animated music video for Year Long Disaster's 2008 single "Leda Atomica",[9] and has performed live with the band in Atlanta, Georgia.

[10] In 2022, a new film from Maiellaro entitled Pastacolypse was reported to be in the works at Bento Box Entertainment and would stream exclusively on Tubi.

[12] In 2024, Maiellaro launched a YouTube series titled Meat Kingdom, in which he interviews friends and colleagues who have worked with him on projects such as Aqua Teen Hunger Force and 12 Oz.