- Accidental Innuendo: From the episode "Deep Sea Tour": "Simple—you suck."
- "Funny Aneurysm" Moment: In "The Sackless Games", the final event is a luging competition (where Weasel and Baboon ride brothers with Luge for a last name). At the end, the Red Guy says "I tried to warn them that the luge is the most dangerous event in sports, but they would not listen.". 11 years later, Nodar Kumaritashvili died in a luging accident hours before the start of the 2010 Winter Olympics.
- In "I Am Bush Pilot" I.R. almost crashes the airplane he and Weasel are piloting into a mountain. This would be far less funny years later after the Germanwings plane crash in the French Alps in 2015.
- Growing the Beard: The second season is seen as an upgrade to the first season by some due to the inclusion of the Red Guy, the improved animation and Weasel becoming less of a Hero Antagonist and more into the smarter and saner of the two friends.
- Ho Yay: "I.R. Do" has Weasel resort to dressing himself as a bride and marrying Baboon when Baboon is despondent to learn that his bride has left him at the altar for a German hairless Chihuahua.
- Jerkass Woobie: I.R. Baboon had more than a few moments of being antagonistic towards Weasel, but it's hard not to pity him for his longing to gain the same recognition and praise his smarter rival gets.
- Suspiciously Similar Song: Weasel's song from "I R Mommy" sounds like "Lookin' Out My Back Door" by Creedence Clearwater Revival.
- What an Idiot!: From "Power of Odor": If a methane smog is large enough to turn a whole city uninhabitable, who in their right mind would throw a lit match in the center of the cloud?
YMMV / I Am Weasel