Complaints over the Gandhi character led to MTV pulling the show from airing in the United States, and subsequently the show's cancellation.

In "Raisin the Stakes", J.F.K.'s incoherent mumbling after falling through the skylight is clearly normal speech played in reverse. When recorded and re-reversed, he says: "I am talking backwards, and telling you to watch Clone High, and for us to win an Emmy, I'm saying that backwards, 'cause it's sneaky!"

All five of the main characters are a clone of a historical figure that met with a violent death: Abraham Lincoln, Mohandas Karamchand Gandhi, and John F. Kennedy were assassinated, Joan of Arc was burned at the stake, and Cleopatra committed suicide by snake bite.

In the prom episode (episode thirteen), when Joan of Arc's breasts are visible for a split second, where her nipples should be, are the words "nice try".

Teen Wolf makes a cameo in each episode.

Genghis Khan's t-shirt (often obscured) reads "Skrew Tibet!"

In the script for the pilot, Mr. Butlertron was named "Mr. Belvetron" and programmed to take on the characteristics of the sitcom character Mr. Belvedere (1985), which is the reason he calls everyone "Wesley" (most noticeably Gandhi).

The episode, "Raisin the Stakes" contains multiple subliminal messages. DNA Dan, the school's mascot, appears saying, "Let's Go to the Dark Side". At the PTA meeting, when Principal Scudworth starts talking, a picture of him and the words, "Scudworth is you're favorite character!" flash across the screen. After the first commercial break, where many of the characters are sitting in J.F.K.'s van smoking raisins, a picture of an anthropomorphic raisin smoking a "human doobie" can be seen in one frame. When J.F.K. is sitting in his wheelchair with a broken leg, the message, "I Buried Ponce" flashes across the screen (a reference to the phrase, "I buried Paul", which can allegedly be heard at the end of the Beatles' "Strawberry Fields Forever"). During Abe's hallucination with the real Abe Lincoln, a cartoon re-creation of the famous painting of Joan of Arc flashes across Joan's face as she yells, "Aaa-eee-aa-ee-abe". As Ghandi and the dragon fly over the school at the end, the phrase, "For more information about raisins, consult your local library" flashes across the screen.

The last five episodes were never aired in the U.S.

A dolphin appears in every episode, sometimes in the background, and sometimes as a plot point.

Despite being an MTV/Teletoon Co-production, the show was co-produced with Touchstone Television, marking as Disney's third adult animated series after The PJs and Clerks: The Animated Series.

All the figures in the background shots are based on historical figures: These include Julius Caesar, Jesus Christ, Nostradamus, Sir Isaac Newton, Catherine the Great, Eva Perón, et cetera.

In "Raisin the Stakes", when Cleo and Abe were on top of the cafetorium during the PTA meeting, during one frame of animation, you see them both naked.

There are dolphin-noises or an actual dolphin every episode.

The show is meant as a parody of teen dramas and sitcoms of the 1980s, where they had several "themed" episodes.

This is one of three productions in which Genghis Khan and Abraham Lincoln appear together as characters, in spite of the fact that Lincoln was born 582 years after Khan's death. The others are Star Trek: The Original Series: The Savage Curtain (1969) and Bill & Ted's Excellent Adventure (1989).

Cloudy With a Chance of Meatballs character Sam Sparks was named after a real life intern who worked on the show as part of the crew.

At least 6 actors from the TV show Scrubs (2001) are part of this cast.