[1][2] Sealab 2021 is one of the only four original Williams Street series that premiered in 2000 before Adult Swim officially launched, with the others being Aqua Teen Hunger Force, The Brak Show, and Harvey Birdman, Attorney at Law.

Adam Reed and Matt Thompson, the creators and writers of Sealab 2021, came up with the idea for the show in 1995 while they were production assistants for Cartoon Network.

Five years after quitting Cartoon Network, the two went back to the original tape, this time making the characters do what they wanted.

There are occasional running gags, such as the "Grizzlebee's" restaurant chain, a parody of Applebee's and Bennigan's, the character of Sharko, and Prescott, the half-man, half-tentacle monster "from the network".

[9] Paul Di Filippo of the website Sci Fi Weekly, in his review of the Season 3 DVD, felt that general fan opinion of the show declined sharply following the death of Harry Goz (the voice of Captain Hazel Murphy) during Season 3.