The Subtitle of the film being "The First Epic Film" is a nod to how each book had "The [blank] Epic Novel" by Pilkey's name.
The image of Captain Underpants standing heroically on top of a building on one of the promo posters is one towards the very first cover of the book series.
The comic introducing the Captain's origin and superpowers is a slightly tweaked version of the RetconnedSuperman parody one George and Harold give him in book five.
It also has bystanders exclaim: "It's a bird!" "It's a plane!" "It's an egg salad sandwich!", a homage to Superman from the first book... except this time what they're looking at actually is a giant evil egg salad sandwich.
Captain Underpants's boast of "Faster than a speeding waistband!" "More powerful than boxer shorts!" "Able to leap tall buildings without getting a wedgie!" is exclaimed while one of his comic book villains wedgies themselves trying to attempt the latter. He also makes his declaration that he fights for "Truth, Justice...and all that is Pre-Shrunk and Cottony!"
Mr. Krupp's introduction has him angrily grabbing and destroying George and Harold's comic immediately after they finish it, referencing Dav Pilkey's childhood experience of his own teachers destroying his drawings and comic books.
Mr. Krupp yells at George and Harold for changing the letters on the school sign that read "Sewage Plant Field Trips are Today" to "Come See My Hairy Armpits". A similar incident happened in the second book where they changed the letters on a furniture store sign from "Come In and See Our Pretty Armchairs" to "Come and See Our Hairy Armpits". George and Harold changing the letters of the school signs is a general Running Gag in the books and later in the TV series.
The final prank of the flashback montage is of Edith, the Lunch Lady opening her fridge and promptly filling the school with bubbles. A similar prank happens in the third book where George and Harold trick the three lunch ladies into flooding the school with green goop via mixing industrial quantities of vinegar and baking soda.
Some of the pictures in George and Harold's treehouse showcase future Captain Underpants villains like Wicked Wedgie Woman and the Bionic Booger Boy. The comic book flip-through also prominently features a pair of aliens that strongly resemble the evil lunch ladies, and has Dr. Diaper's robots on the front cover.
Mr. Fyde appears early in the film as the prior science teacher before being fired offscreen, referencing a subplot from the fourth book where he quit the job due to all the prior books' events convincing him that he was going crazy.
The "Everything Except Fabric Softener" store from book five can be seen as a background gag during Harold's sockpuppet Imagine Spot; so does a billboard for "John's House of Toilets" and shop signs for "Trampoline City" and "Crazy Ed's Extra-Fluffy Pillows", all of which featured in book 7. The Piqua Pizza Palace that everyone in the fourth grade but George and Harold go to in book four is also seen. The building that Captain Underpants enters is owned by Snotco, which first appeared in book six.
Although the circumstances are completely different, the plot point of George and Harold having first become friends in kindergarten was undoubtedly inspired by book 9, which was a Whole Episode Flashback which also established that George and Harold first met in kindergarten.
The books' obsession with Uranus shows up as the basis for George and Harold becoming friends. It also serves as a Chekhov's Gag.
The robots in Harold's Imagine Spot resemble that of Dr. Diaper's two robots in the first book.
Edith the lunch lady, who has a mutual crush on Mr. Krupp, shares her name with Edith Anthrope, a schoolteacher who Captain Underpants saved in the sixth book and was messily kissed by. (Ms. Anthrope is also in the film but her first name is never said.)
While trying to steal the turtle camera from Mr. Krupp and witnessing Krupp and Edith flirting, George comments that "adults don't like-like other adults", to which Harold points out that George probably wouldn't see it much at his home since his parents are married. This is a reference to the books, where it was mentioned in book 9 that Harold's parents divorced when he was a kindergartener.
One of the Krupp's confiscated comic books features Captain Underpants holding open the jaws of the mutant dandelion of the third book.
During the "Saturday" song, George is wearing pajamas with Dr. Diaper's robots and Harold is wearing pajamas with the alien lunch ladies.
George and Harold first hypnotize Mr. Krupp to be a chicken and a monkey before Captain Underpants, which is exactly what they did in the first book.
Captain Underpants trying to help an old lady with her cat stuck in a tree by taking the old lady up to the tree can be seen as one to the seventh book where he (in Melvin's body) helps two old ladies cross the street, only to put them in a tree while saving a little girl's cat up the tree.
The dachshund that tried to eat George and Harold in the 4th book shows up twice in the background.
Mr. Krupp lives on "Curmudgeon Boulevard", the exact same street as his book counterpart as revealed in Book 8.
The carnival and the teachers getting detention (though with a radically changed reason for happening) is lifted right out of Book 2. During said carnival, cutouts of Sulu and the alien lunch ladies can be seen.
The comic George and Harold create about Professor Poopypants is titled "Captain Underpants and the Perilous Plot of Professor Poopypants", which is the same title of the fourth book in the series, which was also Poopypants’ debut.
During the Flip-o-Rama segment, Harold rips one page down the middle by accident from flipping too hard, much like many, many readers have to the books. He also steps on the page, leaving sneaker prints that resemble the outlined hand shapes that told readers where to put their hands to flip the pages.
When trying to talk Professor Poopypants out of his wrath, George and Harold try to act like having a silly name would be awesome, like if they were named "Fluffy Toiletnose and Cheeseball Wafflefanny". In the fourth book, Poopypants's plan was to force the world into changing all their names into silly ones, and the quoted names were the ones George and Harold received.
Professor Poopypants’ “Oh really, Oprah? Is that my problem?” line could be a reference to one of two things: The “W” first name on the “Name-Change-O-Chart 2000” being “Oprah”, or the line in Book 10 after Professor Poopypants’ faked death where the Oprah Winfrey Network is listed as an example of misdirection.
Captain Underpants gains superpowers due to ingesting something from the lunch lady, though the circumstances are completely different.
After Captain Underpants gains superpowers, he fires his underwear at Poopypants, with his cape serving as Scenery Censor. Thankfully he has unlimited underwear superpowers, but it references a gag from the first book where he used the same tactic but had only one pair, his modesty preserved by wearing a barrel.
During the climax, George accidentally shoots Harold's hand, making it giant, while trying to shoot the shrunken Captain Underpants back to normal size like in the fourth book.
The comic book Captain Underpants is seen reading at the end features Dr. Diaper, the villain from the first book.
George and Harold's final prank was sending love letters to Mr. Krupp and Edith, making them think the letter was sent by the other, similar to what happened in the fifth book where George and Harold tricked Mr. Krupp into signing a marriage letter to Ms. Ribble.
The radioactive leftovers from the destroyed Turbo Toilet 2000 turns a nearby toilet dump into an army of Talking Toilets, complete with their chant of "YUM YUM, EAT 'EM UP!"
Of course, the movie wouldn't be a faithful adaptation of the books if it didn't end with the last line of dialogue being "Here We Go Again!!"
The credits illustrations are LOADED with these, with at least one or two thing from every book in the series, from the first to the last. Listed all down in order are:
Dr. Diaper’s robots being squashed by Captain Underpants falling over them while they try to steal the Crystal, in a Call-Back from a similar scene in the movie where Captain Underpants stops a duo of robbers.
George and Harold using a pole to quickly write “I will not make comics” multiple times at once in the chalkboard as in Book 2.
Captain Underpants, George, and Harold smashing over the Dandelion of Doom and falling in a replicated manner from when they were in the same situation in Book 3.
George and Harold being intimidated by the Wicked Wedgie Woman from Book 5.
Professor Poopypants riding his Tippy Tinkletrousers time-traveling robo-pants and shooting from the Freeze-Ray 4000, all from Books 9 and 10.
The evil lunch lady aliens, Zorx, Klax, and Jennifer, shooting the city from their UFO as in Book 3.
George, Harold, and Captain Underpants being chased by Mr. Meaner / Sir Stinks-a-Lot from Book 12.
Robo-George and the Harold-2000 destroying the city as in Book 5.
In a Freeze-Frame Bonus during the transition from the previous Gag to the next, an angry human cafeteria lady from Book 3 is seen.
The school teachers mad at George and Harold for having their chairs stuck in their backs as in Book 2.
Melvin in his Glow-in-the-Dark Time-Traveling Robo-Squid Suit grabbing Captain Underpants, George, and Harold. However, unlike the exact scene in Book 11, George and Harold are not holding Sulu and Crackers’ eggs.
Captain Underpants having his cape stuck on the back of a truck. In book 1, the truck is driven by Dr. Diaper’s robots, but the credits of the movie do not show the driver.
And finally, George and Harold being shocked at the school kids coming out of the cafeteria as Lunchroom Zombie Nerds in an exact reenactment from the scene in Book 3.
During the actual rolling credits, a few drawings adapted from the books can be seen.
A drawing of Crackers is seen.
A drawing of Melvin saying one of his catchphrases of the books, "I'm telling", is seen.
A drawing that makes better sense in context of the books has the Inedible Hunk from the Captain Underpants comic shown in the first book being flushed down a toilet as exactly shown in the comic.
A drawing of Sulu can be seen.
A drawing of Mrs. Singerbrains can be seen
One of George and Harold's pranks mentioned in the first book by Mr. Krupp was rigging the school intercom system to play "Weird Al" Yankovic songs for six hours straight. The man himself co-wrote and performed the movie's theme song.
Two of the deleted scenes had references to the first book. The first one had Mr. Krupp basically blackmail George and Harold into becoming his servants, otherwise they would immediately be put in separate classes. And the second had the boys switch the incriminating video of them on the Tattle Turtle with a Boomer the Purple Dragon Sing-a-Long tape.
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