South Park's creators Trey Parker and Matt Stone had written about 850 pages worth of material for the game which included nearly every character and element from the series. They were urged by the developers to cut down the material and possibly release some of it as downloadable content, however the two disagreed on the idea and after also hearing disapproval from fans over it, Parker said "and I agree... fuck that." Any material cut form the game may however be reused for the television series.

According to the commentary for the South Park episode "Insecurity", one of the ideas for the game would have been to sneak into other people's homes and get past their security systems. This was before Trey Parker and Matt Stone went with the idea for the RPG Stick of Truth game.

When the game's original publisher, THQ, went bankrupt, South Park's creators didn't know about it until reading about it in the news. They were really excited when they heard that Ubisoft had picked up the rights to the game.

The achievement/trophy "Heisenberg" requires the player to defeat the Meth Tweekers while wearing the Evil Cartman goatee and the bald cap. This is a reference to the TV series Breaking Bad.

Several scenes, mostly involving abortions and anal probing, were censored in the European console releases. Instead of simply removing the scenes, these sections of the game are replaced by a picture of Michelangelo's David face-palming in front of a European flag, with descriptive text of what the scene would have entailed.

The scenes are also censored in the Australian release, and instead feature a picture of a crying koala.

The PC release, however, was only censored in Germany, Austria, Australia, Singapore, Hong Kong & Taiwan, with all other regions, including the UK, receiving the uncensored version.

Matt Stone and Trey Parker have stated that The Elder Scrolls V: Skyrim, Earthbound, Paper Mario, and The Legend of Zelda were all key influences to the direction that The Stick of Truth took. Parker said that he loved the feeling of Earthbound, in being a kid in a big world, and playing within something larger than initially perceived.

Attempting to leave the room when confronted with the task of Spoiler:removing a Snuke from Mr. Slave's asshole will cause Spoiler:an explosion to occur, the credits to play, and results in the player receiving a game over.

Certain elements from the game were mentioned in Gameinformer, but never made it into the finished product of the game. Some of them were reworked and scrapped all together. There were plans for showing the kingdoms of the Underpants Gnomes and Crabpeople, fighting hippies, a sidemission where the new kid has to rescue Cartman's Polly Prissy Pants doll from the ginger kids, and an enemy dragon (that may have been a boss at one point in the game) called The Thing.

It's possible to use the Mr. Slave summon while Spoiler:you're inside of him.

The Elf Blade is a possible reference to Link's Master Sword from The Legend of Zelda series.

The Bank Teller is a secret optional enemy in the game. The New Kid simply needs to use Gnome Dust to shrink down and go through a well hidden hole behind the left of his desk in the bank. The Bank Teller is ridiculously easy to fight, as he has no Shields, Armor, and no Special Attacks. His melee attack consists of kicking the New Kid or his buddy. Once defeated, the New Kid can loot him for all the money that was invested into him over the course of the game, as well as an extra $10 for each $20 invested. After defeat, The Bank Teller remains unconscious until the player leaves the bank, at which point he'll despawn like any other enemy.