She is the daughter of cinematographer Caleb Deschanel and actress Mary Jo Deschanel. Her sister Emily Deschanel is also an actress.

Noted for her unconventional beauty and a chameleon-like ability to change personas to suit a given role, Deschanel has steadily expanded her Hollywood profile, appearing first in Mumford (1999) and also recently as Trillian in the movie adaptation of Douglas Adams's science fiction series The Hitchhiker's Guide to the Galaxy (2005).

Deschanel has appeared on the talk show circuit (including Jay Leno and Letterman) and presented film industry awards. Her TV portfolio also includes Frasier and various MTV clips including Offspring's video "She's Got Issues".

She appears with fellow actress Samantha Shelton in a cabaret act named If All the Stars Were Pretty Babies.

The name "Zooey" was inspired by the male character of the same name in J. D. Salinger's novel Franny and Zooey.

Filmography:
Surf's Up (2007) (filming) (voice) .... Lani
The Assassination of Jesse James by the Coward Robert Ford (2006) (post-production)
Flakes (2006) (post-production) .... Miss Pussy Katz
The Go-Getter (2006) (post-production) .... Kate
Live Free or Die (2006) (post-production) .... Cheryl

Failure to Launch (2006)
Once Upon a Mattress (2005) (TV) .... Lady Larken
Winter Passing (2005) .... Reese Holden
The Hitchhiker's Guide to the Galaxy (2005) .... Trillian
Eulogy (2004) .... Kate Collins
Elf (2003) .... Jovie
House Hunting (2003) .... Christy
It's Better to be Wanted for Murder Than Not to Be Wanted at All (2003) .... Gas Station Girl
All the Real Girls (2003) .... Noel
Whatever We Do (2003) .... Nikki
Abandon (2002) .... Samantha Harper
Sweet Friggin' Daisies (2002) .... Zelda
The New Guy (2002) .... Nora
Big Trouble (2002) .... Jenny Herk
The Good Girl (2002) .... Cheryl
Manic (2001) .... Tracy
Almost Famous (2000) .... Anita Miller
... aka Untitled: Almost Famous the Bootleg Cut (USA: director's cut (DVD title))