I tried to keep this list to “Team-Ups” or “Cross-Overs” and not “Guest Appearances.”
i.e: Avengers #239 (vol I), the Beast and Wonder-man appeared on the David Letterman Show. To me, this counts as a “Guest Appearance” rather than a “Team-up.”

(This list will include affiliate links that I may [hopefully] receive compensation for)
Here are Geeky Daddy’s Strangest Comic Book Team-ups!
Batman / Elmer Fudd

Elmer Fudd comes to Gotham and he has a few days…TO KILL!
Just kidding, but writer Tom King and artist Lee Weeks did give this unique cross-over a cool ‘noir’ vibe!

New Avengers & The Transformers
If you think the pairing of the Avengers and the robotic aliens of Cybertron sounds pretty goofy….well…you’d be right.
But trust me: the only thing goofier than this pairing is the story. The ending was even goofier…
Godzilla vs. The Avengers

In the late 1970’s, Marvel comics had the publishing rights to Godzilla (and a few of his kaiju friends). In the last couple issues of the series, Godzilla made his way to New York City to see the sights. The Avengers were worried about possible damage from his visit and a resulting battle born of a simple misunderstanding ensued.
Transformers My Little Pony
Somewhere, a Hasbro executive green lit the idea to have these two Hasbro properties team-up.
Whether that was on a dare after a serious session of micro-dosing, who knows.
Batman / Teenage Mutant Ninja Turtles
Batman has actually teamed up with everyone’s favorite ‘heroes in a half shell’ multiple times (at least 5 different mini-series that I am aware of), but my favorite is the Batman Animated series Batman with the animated Teenage Mutant Ninja Turtles.
Transformers / Back to the Future
This amazing crossover gave us the first appearance of Gigawatt, the transformer version of the DeLorean from Back to the Future. That is about all the good I can say about it…

Superman / Aliens (Xenomorphs)

You may be thinking “If Sigourney Weaver could mow down the Xenomorphs, shouldn’t Superman mope the floor with them?”
Well, longtime Superman writer Dan Jurgens employs the often re-used Superman trope of separating Superman from our “yellow sun” to de-power him (Superman his basically a powerful solar panel and requires our sun to recharge his powers) to make this battle last more than a few panels.
Teenage Mutant Ninja Turtles / Ghost Busters
2 of New York City’s greatest quartets team-up to save the multi-verse from utter destruction.
This mini-series was released in 2014 which was also the 30th anniversary of both these franchises.
Eminem / Punisher

Yeah, this happened.
This comic was a “freebie” included in a 2009 issue of the hip hop magazine XXL. But it isn’t free anymore!
The XXL Eminem / Punisher variant issue is now one of the rarest modern comics and often commands $150 for an ungraded near mint copy!
What are some other strange comic book Team-Ups and Cross-Overs?
Let me know in the comments below!
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Be sure to check out some of our other Comic Book related post including Best Captain America Covers, Top Disturbing Superman Storylines and Top Polar Vortex Inspired Super Powered Characters!