Zooey (pronounced /ˈzoʊiː/) Deschanel was born in Los Angeles, California, the daughter of Academy Award-nominated cinematographer and director Caleb Deschanel and actress Mary Jo Deschanel (née Weir). She is of 3/4 Irish descent and 1/4 French descent (her surname means "from the channels" in French). She was named after Zooey Glass, the male protagonist of J. D. Salinger's 1961 novella Franny and Zooey. Her older sister Emily is also an actress.

Deschanel lived in Los Angeles, but spent much of her childhood traveling because her father shot films on location; she later said that she "hated all the traveling[...]I'm really happy now that I had the experience, but at the time I was just so miserable to have to leave my friends in Los Angeles and go to places where they didn't have any food I liked or things I was used to." She attended Crossroads, a private preparatory school in Santa Monica, California, where she befriended future co-stars Jake Gyllenhaal and Kate Hudson