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.

The game was developed long before the Wii U even started development. In an Iwata Asks interview, Masataka Takemoto stated that the team used materials from New Super Mario Bros. Wii. By the time the Wii U GamePad was announced, he considered having four-player cooperative play with an extra player using said GamePad to add blocks.

When enemies dance in sync with both games' music, Pokeys will swap their spikes for flowers for a brief moment. If a Pokey is eaten with Yoshi during this point in time it will be instantly defeated and the Yoshi will lay an egg containing a power-up. The power-up can range from coins to 1-ups depending on how many segments the Pokey had when it was eaten.

The developers tried using Mii characters in the story mode, but thought that it no longer felt like a Super Mario game, so they created other game modes where the player can use their Mii characters.

In an enemy course level, if you defeat the enemy and wait about 30 seconds, Nabbit will appear, steal your prize and then jump off screen. If however Nabbit is being played as in New Super Luigi U or either game in the Switch port, the screen will simply fade to black without anything happening.

On the second loop of the title screen, Luigi won't jump and ground pound with the rest and will look confused, briefly, before turning to run as usual.

New Super Mario Bros. U began as a tech demo, shown at E3 2011, called New Super Mario Bros. Mii. It allowed players to use Miis in all modes. If all four players chose Miis, Player 1 would be dressed as Mario, Player 2 as Luigi, Player 3 as Wario, and Player 4 as Waluigi but with blue sleeves.

While Miis are no longer selectable in all game modes, this concept did make it to the final game in the form of "Boost Rush Mode".