With the development of New Super Mario Bros. 2 and New Super Mario Bros. U happening simultaneously, Nintendo created a "Mario Cram School" to teach developers from outside the core Super Mario team how to design levels. Most of the core developers of New Super Mario Bros. 2 were "graduates" of this program, while New Super Mario Bros. U was developed by the same core team that made prior games in the series.

In the ending cutscene of New Super Mario Bros. 2, the Koopalings carry Bowser by the tail after his defeat while Mario and Peach run home. Due to the strain that rendering a large character like Bowser alongside the models of 9 other characters and a vehicle could cause on the 3DS hardware, Bowser does not use his regular model used in the rest of the game, but rather a set of flat pre-rendered graphics tilted to appear 3D.

The developers originally considered calling the game "New Super Mario Bros. Gold" because of its theme of "one million coins", and the various features surrounding the idea. However, they felt that many of the games levels stood on their own, even without considering the coin collecting elements, and so they decided to emphasize that it still had the classic Mario gameplay by calling it New Super Mario Bros. 2.

When the player enters Coin Rush for the first time, they will receive several informative messages; the second message, "Exchange Coin Rush records with people you meet! Your Mii character and name will be also be exchanged", contains a typo by saying "be" twice in the second sentence. This typo is only present in the US version of the game.