The episode's plot contains a theme of equality and civil rights. "The Mutants Are Revolting" has been interpreted as a political warning against societies with a "disposable class" of people. It has also been interpreted as a statement about the plight of undocumented immigrants, due in part to Leela's secret status as an "illegal alien" in the series (as mutants are not allowed to live on the surface). Mr. Astor giving up his seat on the "lifeboat" for Leela's grandmother and great-grandmother may be a reference to Alfred Vanderbilt, a wealthy passenger on the Lusitania, who gave his life belt to a young woman and her child, though he himself could not swim.
- The song performed by Devo, "Beautiful World", is shown to be sung by Mark Mothersbaugh in concert, but the recording used features bassist Gerald Casale on vocals.
- When Fry crawls out of the Land Titanic, a can of Angry Norwegian anchovies can be seen on the ground. Again, Fry is so close to riches, yet so far.
- This episode is the 100th only if one counts the four Futurama movies as sixteen episodes (four episodes per movie).
The episode has many references to the Bible. The Jewish people (Mutants) are oppressed and someone from their oppressor's side, Moses, fights for them (Fry). Fry also says "Let my people go", which is what Moses says to Pharaoh. The water (Tidal wave) parts when Moses holds up his staff (The crystal).
When the mutants are swept away, Leela's father says 'They're with the C.H.U.D.s now.' This is a reference to the 1984 horror film C.H.U.Ds (Cannablistic Humanoid Underground Dwellers) and to it's sequel Bud the C.H.U.D.
The Westside Pipeway's design and location (under the city) is a reference to the "M-Machine" from the 1927 movie Metropolis.
The scene where the crew delivers the soufflé is a reference to the music from 1977 film Sorcerer.
The Land Titanic has several reference to the actual Titanic
- The Land Titanic sank in 2912, while the actual Titanic sank in 1912.
- On the Land Titanic 2000 souls where lost, and on the actual Titanic around 1500 souls where lost.
- The Land Titanic hit a mailbox and sank, ands the actual Titanic hit an iceberg and sank.
- The Land Titanic was the largest street-going vessel ever built, and the actual Titanic where the largest ship ever built.
- Mrs. Astor is a character on Futurama with a husband names Mrs. Astor who sank with the Land Titanic. Madeleine Astor was a real living person and a survivor on the real Titanic, and a widow of her millionaire husband, John Astor, who sank with the Titanic.
Million Man March
The Million Mutant March is a reference to the Million Man March.
Issac Newton's Law
Fry says "What comes down must back up" a refernce to Issac Newton's Law "What goes up, must come down".
- Dwayne ask Devo to play "Whip It", which probaly is Devo's most famous song
- Devo says: No, play the other one, which is "Beautiful Minds". This could be a parody of the fact that Devo one had two famous songs.