The first-person shooter will see players become one of the last survivors on Earth after its invaded by swarms of aliens, or 'Killer Freaks'.
The touch-screen controller will be used as an additional viewpoint, where in multiplayer one person can send aliens to hunt down and kill others.
"When Nintendo launches a new console, it's always a big milestone for the industry and a great opportunity for creativity," said Ubisoft CEO Yves Guillemot.
"Killer Freaks will make the most of all the fantastic capabilities of the Wii U and provide hardcore players with a gaming experience like no other they have seen or played before."
The new entirely original game is in development by Ubisoft Montpellier, who is also working on Rayman Origins and Beyond Good & Evil 2.
"When we realised the potential of what Nintendo was offering by creating a tactile controller, we were off and running immediately," said managing director Xavier Poix.
"Having that extra screen in the hand of the player allows us boundless innovation that ultimately gives the player a more beautiful game, a faster game interface, a personalised game experience, and so much more."
Assassin's Creed, Ghost Recon, Rabbids and a new sports franchise will also be coming to Wii U from Ubisoft.
Killer Freaks from Outer Space will be a launch title for the Wii U when it releases next year.
More Wii U coverage:
> Wii U announced as new Nintendo console
> Wii U pictures: Nintendo's new controller
> Wii U technical specifications released
> Super Smash Bros. coming to Wii U, 3DS
> FIFA to become Wii U launch title?
View Killer Freaks from Outer Space's first trailer and screenshot below: