- Nate has very Calvin-esque hair. Though this might not be on purpose, as this interview shows.
- In one arc, School Picture Guy wore a lobster suit to a dance with a sign on it saying, "Rock Lobster".
- In a strip that payed Homage to Charles Schulz, Nate's baseball team plays Charlie Brown's team and Charlie Brown congratulates them afterward. Nate walks away saying, "Good ol' Charlie Brown!"
- One arc was basically devoted to Harry Potter, with Nate reading the new Harry Potter book and kids starting a Harry Potter club.
- In one strip where Mr. Rosa asked Nate to run an errand in the teacher's lounge, Nate thought to himself as he left, "To boldly go where no one has gone before."
- During Prank Day one year, Principal Nichols stepped out to the parking lot... and said, "Dude, Where's My Car?"
- During another Prank Day, Nate releases a flying squirrel and a moose in the school.
- One of Nate's "Doctor Cesspool" comics (that the idea of which was re-used for a comic in Big Nate on a Roll) had a patient of Dr. Cesspool's sue him for reattaching his hand where his foot should be, and vice versa. Fans of The Simpsons may recall a moment where Dr. Nick Riviera sees a former patient of his, where the same thing apparently happened.Dr. Nick: Well, if it isn't my old friend Mr. McGreg! With a leg for an arm and an arm for a leg!
- While Nate's writing a romance novel, he says that the lady in the starring role owns a pony named Dusty. Teddy then suggests giving her a pet monkey, in a reference to the book Pippi Longstocking, where Pippi has both a pony and a pet monkey.
- Spitsy is at one time thrown a plush of Garfield by Nate to teach him to attack cats.
Shout Out / Big Nate