There are lots of ways to derail a tabletop role-playing campaign, some more obvious than others. For one thing, they can often start as a serious group of adventurers who just start making silly inside jokes as the sessions continue.
Sometimes the Game Master can derail a campaign by including legendary evil artifacts like the Eye and Hand of Vecna. And sometimes what were intended as minor surprises accidentally have a far bigger impact than intended. This last instance happened in my library campaign.
One of my regular players has a half-orc barbarian with a fondness for axes. I trust her to role-play her character, so I warned her the magic axe she wanted wasn't all it seemed. She didn't care. Orc want axe, orc take axe, orc happy. What I didn't tell her until later was that it is a Berserker Axe. While it increases the odds of hitting an enemy and increases the damage dealt when it does hit, it has a major downside.
This axe is cursed, and becoming attuned to it extends the curse to you. As long as you remain cursed, you are unwilling to part with the axe, keeping it within reach at all times. [...] Whenever a hostile creature damages you while the axe is in your possession, you must succeed on a DC 15 Wisdom saving throw or go berserk. While berserk, you must use your action each round to attack the creature nearest to you with the axe. [...] You are berserk until you start your turn with no creatures within 60 feet of you that you can see or hear.—D&D Beyond item description excerpts
The next chapter of the campaign after the axe was issued is a dungeon delve into an ancient underground complex. I modified a map from Dyson's Dodecahedron and gave the party the original as a relic from their patron. This complex was once a dwarf hall, later taken over by an evil sorcerer who the party's patron once defeated when he was an adventurer. He always thought there were more secrets to be uncovered there, though, and sent the party to explore it again and clear out whoever had moved in during the decades or centuries since then.
Orcs with shiny new axes like to be in the front line when goblins (or anyone else, really) is around. Barbarians can resist a lot of damage just by getting extremely angry. But barbarians in the front lines inevitably take damage. Orc barbarians do not tend to have very high wisdom scores. The inevitable failed save occurred, and carnage ensued.
I was a kind GM, and allowed the other characters a chance to notice that something was wrong with their orc friend. They backed off and the magic users cast spells to blind and deafen the orc until he calmed down. However, this happened again in the next session... twice! fortunately, a new player joined the campaign, and I inserted them as a prisoner rescued from the depths. He was able to break the curse binding the orc and axe. All is well, except now orc still want axe.
