Originally, the show was to be called Normal Show, and two animals (similar to Mordecai and Rigby) would work at a zoo, where the animals would be humans.
Unlike most Cartoon Network shows, this show is known for its use of licensed music. Much of them are usually 1980s, music which was the kind of music, to which Series Creator J.G. Quintel grew up listening.
Sam Marin originally auditioned for Skips, and Mark Hamill originally auditioned for Pops. Marin and Hamill switched roles after their voices didn't sound right for the characters they auditioned for.
Prototypes of the main characters debuted in J.G. Quintel's animated shorts The Naive Man from Lolliland (Pops) and 2 in the AM PM (2006) (Mordecai, Benson, and Pops).
Thomas the intern's shoes resemble those of the famed video game character Sonic the Hedgehog which Thomas's voice actor voices as well. Roger Craig Smith.
Before this show, the series creator, along with the voice actor for Benson made a video where their characters take candy with acid in it and hallucinate themselves as a blue Jay (Mordecai and Benson). The video is called "2 in the A.M. P.M.
A list of running gags on the show include: Muscle Man making jokes about his mother. Pops mistaking lollipops and other candy for money. Benson telling Mordecai and Rigby to clean their mess, and tells them they will be fired if they don't. Mordecai acting weird and shy around Margaret, due to his crush on her. - Rigby getting punched by Mordecai every time he says or does something mean, selfish, or stupid. - Skips having seen something before.
This show was inspired by The Simpsons (1989) and Beavis and Butt-Head (1993), and Quintel credited the stylistic elements of Joe Murray's Rocko's Modern Life and Camp Lazlo as working their way into his style.
The show is based on J.G. Quintels student film "2 in the AM PM", which was about two gas station clerks who take acid trips after eating two pieces of acid filled candy. The first clerk is played by J.G. Quintel, the Creator of this show, and he is named after him as well. The second clerk is played by Sam Marin, who plays Benson, and is named after him. The short never aired on television, due to having a ton of swear words, but is on YouTube though.
The first Cartoon Network show to pass eight seasons, the second will be Adventure Time (2010), which will air sometime this year. This show is the third longest running series on Cartoon network.
The Warlock, seen in season three, episode fourteen, "Fortune Cookie", resembles the warlock from Big Trouble in Little China (1986). Both characters are played by James Hong.
Despite Muscle Man and High-Five Ghost having been fired on season two, episode fourteen, "Temp Check", they reappear in the next episode with no explanation.
There have been many scenes that resemble scenes from the Star Wars saga. In season seven, episode twenty-nine, "The Button", Benson hallucinates himself stuck on the railings underneath Cloud City, like Star Wars: Episode V - The Empire Strikes Back (1980), and in season seven, episode thirty-five, "VIP Members Only", Mordecai, Rigby, Mitch, and Fives fall into a pit with skeletons and fight a monster, a lot like the Rancor pit in Star Wars: Episode VI - Return of the Jedi (1983). Skips is voiced by Mark Hamill, who plays Luke Skywalker.
In the pilot episode, "The Power", Mordecai and Rigby smash a hole in the wall, to which Rigby says "How in the 'h' are we gonna fix this 's'?" in the DVD version. The broadcasted version says: "How in the 'heck' are we gonna fix this 'stuff'?"
Although Rigby's dad is shown being nice in season five, episode thirteen, "The Thanksgiving Special", in later episodes, he is shown as being a rude jerk who cares little about Rigby, and only about his car.
Pops is the only character not to threatened to be fired. Benson almost fired Muscle Man, Mordecai, Rigby, and high-five ghost, along with Skips for no reason, on season four, episode thirteen, "Firework Run".
Mordecai, Rigby, and Benson never wore clothes, except in special occasions, such as parties, missions, and dates whatsoever. The same goes for Skips, who is shirtless most of the time.
In season one, episode five, "Free Cake", Mordecai tells Rigby to stop digging through the trash. Racoons, like Rigby, are known to dig through the trash.
The character "Party Pete" from season two, episode eight, is very similar to an adventure time character named "Party Pat". The creators have said there are no connections between the two characters.
The season four opener, "Exit 9B", aired on October first, which was Cartoon Network's 20th Anniversary along with Julie Andrews' seventy-seventh birthday.
The trivia item below may give away important plot points.
In season three, episode seventeen, "Eggscellent", it's shown that Rigby is allergic to eggs, and that he can fall into a coma. Yet, in season four, episode ten, "One Pull Up", he is shown eating eggs out of a blender.