Isekai is one of the most creative and expansive genres in the world of anime - which means that some of the premises can get extremely weird. Most of the craziest isekai concepts come in light novels or manga like I Was Reincarnated as a Hot Spring in an Alternate World, and I'm way too effective, which is about a dude getting reincarnated into a hot spring, and The Ride-on King, which follows a Vladamir Putin knockoff on his journey to ride magical creatures. There are also funny isekai anime plots that can be found in shows like Kemono Michi: Rise Up, an anime about a wrestler who opens up a pet shop in another world.
There are some other isekai manga that are truly bizarre, like Isekai Transporter, an independently produced parody manga about a truck driver who takes out the people who are supposed to be reincarnated into new worlds, and "Panties Reincarnation. I’m a Pair of Panties, so What? - which is pretty much exactly what it sounds like. However, this list is going to stick to officially published material that's been listed on MyAnimeList.
The world of isekai is as deep as it is strange, and new series are cropping up every day. Which one is the weirdest isekai anime? That's up to you.
A man who is obsessed with vending machines is crushed by one as he tries to protect it from crashing to the ground. He's reincarnated as a vending machine in a fantasy world. Though he wants to see what the world has to offer, he's unable to move or talk, because, well, he's a vending machine. Help comes in the form of an adventurer named Lammis who agrees to carry him around on her back, granting his wish and setting the stage for vending machine themed adventures.
While travelling to an onsen, Atami Kusatsu gets into an accident and loses his life. He's reincarnated into a fantasy world, not as a person but as an onsen. This seems like it would be entirely unpleasant, but there are some perks - the healing nature of his steamy water attracts a wide variety of beautiful women.
Thanks to a clerical mishap, a teenage boy named Riichi is reincarnated as a succubus. This extremely sexual species survives off of what's called "man's life essence." Use context clues and you can probably guess what that is. Riichi is straight, so he adamantly refuses, claiming he'd rather starve. It turns out that he can also survive off of cow's milk, but there are no cows - the people behind his reincanation offer him a superpowered cow to ease his burden.
Is this a thinly veiled excuse for ecchi? Abosolutely, but it's still funny as hell.
If most people got the opportunity to be reincarnated as a character from Dragon Ball, they probably wouldn't pick Yamcha - but that's exactly what happens to the protagonist of Dragon Ball: That Time I Got Reincarnated as Yamcha!, when he trips trying to sneak a peek at a girl's panties, loses consciousness, and wakes up in the world of his favorite series. He decides that he isn't going to take Yamcha's poor circumstances lying down - instead, he's going to change his fate for the better.