[6] In 1994, Deschanel made her feature film debut in the romantic comedy-drama It Could Happen to You, on which her father worked as chief cinematographer.

In 2005, Deschanel was cast as Dr. Temperance Brennan on the Fox crime procedural comedy-drama Bones, based on the novels and the career of forensic anthropologist and author Kathy Reichs, created by Hart Hanson.

[7] In recent years, her passion for animal welfare has led her to providing the narration for My Child Is a Monkey and serving as an associate producer on the documentary film How I Became an Elephant.

[14][15] Deschanel was raised Roman Catholic but is no longer practicing and has expressed agnostic views, saying "I am more of a spiritual person, if anything, and I am of the belief that we don't know, and I'm not going to pretend that I do.

"[16] On September 25, 2010, Deschanel married It's Always Sunny in Philadelphia actor and writer David Hornsby in a small private ceremony in the Pacific Palisades area of Los Angeles.

[20][21] In 2015, Deschanel filed suit against Fox alongside Boreanaz, Reichs and Bones executive producer Barry Josephson, claiming they were cheated out of their share of series profits.