The Horton quote "I meant what I said, and I said what I meant: An elephant's faithful one hundred percent," is actually from "Horton Hatches the Egg", another Dr. Seuss story featuring the enduringly faithful elephant.
The Mayor receives a goldfish in a fishbowl from a Who who looks remarkably like the Cat In The Hat (he is only seen twice, briefly - once from behind, and later from a distance - and his hat has blue stripes instead of red). Later, just before the first attack by Vlad, the Mayor is resuscitating the fish. When the fish lands back in his bowl, he leans on the side of the bowl just like the goldfish in The Cat In The Hat.
This quote, which was spoken by Katie (Joey King): "In my world, everyone's a pony, and they all eat rainbows, and poop butterflies," is often incorrectly attributed to Dr. Seuss. In fact, the line was written for this film. The quote and the character of Katie were not created by Dr. Seuss, and were created after his death.
When the Mayor is showing JoJo the portraits of their family, the last one is of a caveman, who is painted on a set, evidenced by the lights at the top, and creatures hanging from the ceiling by string.
The only computer animated film based on a Dr. Seuss book not produced by Illumination, as they would produce the future films The Lorax (2012) and the upcoming How the Grinch Stole Christmas (2018) and The Cat in the Hat (2021), not counting Green Eggs and Ham (from Sony Animation).
Amy Poehler's character is named Sally O'Malley, which is also the name of a recurring character on Saturday Night Live (1975), played by Molly Shannon. Both Poehler and Shannon got their careers started on Saturday Night Live (1975).
In the scene, where the Mayor (Steve Carell) consults Dr. Mary Lou Larue (Isla Fisher) about what would happen if Whoville was a tiny spec in space, you can see that Dr. Larue is holding up a piece of paper. On that paper, the first paragraph is just random typing. However, the following paragraph, it reads: "Clerk Maxwellies which othe machines, ranging fromag-neticles variety. Aside tranging. Electrodynamics at rea of theorology of the for can ever..."
The Who are similarly designed to the Grinch, which Jim Carrey also played. You can also hear the quote "we like it a lot". It is also said in Dumb and Dumber (1994), where Jim Carrey also plays one of the main characters, but the difference is that in Dumb and Dumber (1994), Jim says "I like it a lot".
Originally Wallace Shawn, Experienced Voice Actor Jim Cummings, Tara Strong, Stephen Root, Austin Pendleton, Alan Tudyk, John DiMaggio, Michael McShane, and Jeffrey Garcia were going to appear providing voice cameos but were sadly dropped in the film.
The first theatrically released animated film for Jonah Hill. Later he'd go onto voice Snotlout Jorgenson in the How to Train Your Dragon films, Hal Stewart/Tighten in Megamind (2010), Green Lantern in the LEGO Movie films, and Carl the Talking Sausage in Sausage Party (2016).