Trey Parker cited EarthBound (1994), Paper Mario (2000), and The Elder Scrolls V: Skyrim (2011) as his main inspirations behind the game's RPG mechanics. The decision to have a silent protagonist was drawn from "The Legend of Zelda" series.
When making a class selection, Cartman will make different (and racist) remarks for certain classes depending on what New Kid/Douchebag's skin color is. For example: Having a "spray-tan" skin color and highlighting Jew Class will make Cartman remark: "A Jew from New Jersey, just like Kyle's mom."
In an episode of the TV show South Park, Butters angrily asks why anyone would want to preorder a video game. His rant was quickly followed by an ad for the Stick of Truth with the phrase "Preorder now!"
The short banjo sting from the post-commercial breaks in the actual show plays whenever a save file is loaded.
Nothing from the E3 2012 trailer (while the game was under development with THQ) appears in the final game. This included: Mr. Garrison dying, vampire kids and crab people as enemy opponents (only one crab person appears and vampire kids show up in a couple of cutscenes), and a giant version of Clyde.