So, I'm still a fledgling DM, and when I was playing Lost Mines of Phindelver, with my older brothers. And oh boy, were  there have been multiple times I can count when my brother's did something that were not expected in that campaign. 

Some hilariously infuriating, and others I kinda rolled with, because I liked the idea.

What was your favorite time(s) your players screwed up your plans?

When my players massacred this

https://www.dndbeyond.com/monsters/505357-tiamat-tarrasque-dracolich

Quote from Bubbub25 >>

When my players massacred this

https://www.dndbeyond.com/monsters/505357-tiamat-tarrasque-dracolich

 Holly balls.  

And the immediately after they regained their hp, took out 3 of these

https://www.dndbeyond.com/monsters/459152-titan-crab

And somehow tamed this

https://www.dndbeyond.com/monsters/430788-baby-tarrasque

Quote from Bubbub25 >>

And somehow tamed this

https://www.dndbeyond.com/monsters/430788-baby-tarrasque

 Hombrew campaign?

Yes

What levels were they?

50

When the wizard successfully gets a polymorph to land on the flying blue dragon and it plummets to its death in the form of a blue whale before it inflicts any damage on the group.... yeah.

Quote from Grebeir >>

When the wizard successfully gets a polymorph to land on the flying blue dragon and it plummets to its death in the form of a blue whale before it inflicts any damage on the group.... yeah.

 That’s a lot of falling damage....

which maxes at 20d6, which is 20-120 damage, which is less than a blue dragons health...

something else must of happened first. But since the post didn’t say “wounded” blue dragon, I am operating under the assumption he was at full health. But then since it didn’t inflict any damage yet... I also wonder how it was wounded and so high up first, and how the party noticed it first to blue whale drop it from 200+ feet up.

We were playing Curse of Strahd and, deciding to be nice, I gave them a magic item that could cast Raise Dead once, and greater restoration twice. Pretty much immediately after getting out of the dungeon where they got this item, they decided to use it on an inconsequential NPC who's death was part of the motivation of another, far more important NPC. And they even had the guts to ask me "Do you think we should do this?"

So I ran a heist adventure where three players, a human monk, a goblin barbarian who is a great roleplayer, and a halfling cleric who's a little shy about playing, infiltrated an airship to steal a key magical part. What they didn't know was (a) an armored villain called the Iron Knight was onto them and (b) when they stole the part, the ship would collapse (everyone aboard had Tokens of Feather Fall, like life preservers).

So, after navigating a Star Wars style trash compactor and fighting through a clan of wererats, they came upon a split: a hall full of clockwork guards or a dark, twisty pipe. The goblin rolls up to the clockworks, bold as brass, and tells them he's just maintenance. I tell him to roll Deception. The total is over 20.

Cool! This seems like short-term gain, long-term loss for the party, since the clockworks won't let the others through so the party is split.Feeling betrayed,  especially since the goblin has stolen other prizes before, the other two party members head into the pipe, where an ooze has dropped from the ceiling. Separated from their strongest fighter, they're about to go down. A few rounds have passed, so I switch back to the goblin.

The goblin strolls in, dodges some piston traps, and find himself in the room with the part...and alone with the Iron Knight. Initiative is rolled, and the goblin wins. He hates the Iron Knight, who's rabidly anti-goblinoid. This is going to be an amazing fight.

Then he says the last thing I was expecting.

"I'm gonna grab the part and run."

I go silent for a second. What should I do? Then I realize what a cool moment this is for the players, and I grin...and stick to the plan.

The ship explodes.

And down they fall, drifting via Feather Fall into a small back courtyard in the city. The Iron Knight is gliding down, sword out. "You and your friends will pay for this, greenskin!" he yells.

Then, an even bigger surprise.

"I'm going to cast this spell," says the cleric, the shy player who almost never speaks up except on her turn. "Pass without trace."

It was so awesome I didn't even make them roll initiative, but the stealth DC to escape while in plain sight was a 20 with disadvantage. They made it anyway. And the Iron Knight was left behind, raging, to appear another time. That might have been the greatest D&D game I've ever played. I thought they'd all go in together. I thought they'd fight before taking the part. I thought this would be the showdown with the Iron Knight. But it turned out even cooler, because they made it happen.

I loved those players.

P.S. The goblin did eventually get his revenge on the Iron Knight in a brutal and emotional street duel, but that's a story for another time.

Also don't blue dragons have an ability where they can automatically make 3 saves a day (at least the bigger ones that would be appropriate for a wizard with Polymorph)?

So in the third session of our Acq Inc campaign, I offered the party a chance to buy a snugglebeast from a random item vendor (from the Griffons Saddlebag, wondrous item that basically replicated the effect of a song of rest.) in under an hour they started a snugglebeast MLM, then decided to hire someone to make knockoff versions and launch Build-A-Beast LLC...

Quote from NaivaraArnuanna >>

So I ran a heist adventure where three players, a human monk, a goblin barbarian who is a great roleplayer, and a halfling cleric who's a little shy about playing, infiltrated an airship to steal a key magical part. What they didn't know was (a) an armored villain called the Iron Knight was onto them and (b) when they stole the part, the ship would collapse (everyone aboard had Tokens of Feather Fall, like life preservers).

 

This triggered me.  Sometime in 2e in a Planescape campaign we were running a module called The Eternal Boundary.  If you've ever read it, in the bad guy's lair, there is a big shiny gem, that, if you steal it, turns off the lair's protective force field and exposes the whole thing to the Elemental Plane of Fire.

One of the players was a Kender.

I learned some valuable lessons about DMing that day.

I was DM-ing a game with a bunch of friends who had never played the game before.

Here's where I messed up: I made all of their characters level 20 the minute they got in the game to make it more fun with all of the unlocked possibilities.

Here's where they messed up things for me: They became straight-up murderhobos and killed the main villain, who was then in disguise as a villager to listen in on the plan they were creating.

Worst part? It was a whodunnit, they were halfway into the game, and all other characters had established alibis when the crime occurred. 

"HAha! Now that I have the super whatszit I can rule the kingdom!!"

"We didn't say we gave it to him..."