The broadcaster's new selection of US acquisitions also includes Dreama Walker (The Good Wife), Krysten Ritter (Breaking Bad) and James Van Der Beek's (Dawson's Creek) comedy Apartment 23.
Deschanel's New Girl follows the story of Jess Day, a quirky woman who after recently splitting up with her boyfriend, moves into an apartment with three men.
Apartment 23 features Walker as country girl June, who has to cope with her life being turned around in New York and her crazy flatmates, played by Ritter and Van Der Beek.
The Napoleon Dynamite animation is a direct spinoff from the cult movie and features the original cast of Jon Heder, Efren Ramirez, Aaron Ruell and Jon Gries.
Jonah Hill's animated comedy Allen Gregory, which is based around the life of a precocious 7-year-old, will also be coming to the channel.
"New Girl and Apartment 23 will add to E4's reputation as the home of the best of US comedy," said Channel 4's chief creative officer Jay Hunt.
Watch a trailer of New Girl below:
Watch a trailer of Apartment 23 below:
Watch a trailer of Napoleon Dynamite below: