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). Her mother is Irish American and her grandfather was French. She has one younger sister: actress, songwriter and musician Zooey Deschanel.
Deschanel is a vegan and a committed supporter of animal rights causes. She can be seen in an Access Hollywood video at the book launch event of Karen Dawn's Thanking the Monkey: Rethinking the Way We Treat Animals, discussing how vegetarian and vegan diets help the environment, and a video on the homepage of the book's website talking about the importance of animal rights. She graduated from Boston University's Professional Actors Training Program with a Bachelor of Fine Arts in Theater.
She married actor/writer David Hornsby on September 25th, 2010. On March 31st, 2011 it was announced the couple were expecting their first child during the fall. Her son Henry Hornsby was born on September 21st, 2011 (also her father's 67th birthday). Deschanel's pregnancy was incorporated into Bones. She is the older sister of actress, singer, and songwriter Zooey Deschanel. On December 5, 2014, Deschanel announced she is expecting her second child.
Deschanel made her feature film debut in 1994's It Could Happen to You. Her next notable role was in Stephen King's Rose Red in 2002. She then appeared in Cold Mountain, The Alamo and Glory Road and was named one of "six actresses to watch" by Interview Magazine in 2004.
After starring in 2005's Boogeyman, Deschanel landed the role of Dr. Temperance Brennan on Fox's Bones, a series based on the heroine in the novels of real-life forensic anthropologist Kathy Reichs. She has been playing this role in Bones for 11 seasons. For her performance she received a 2006 Satellite Award nomination, a 2007 Teen Choice Award nomination, a 2009 Ewwy Award win and has served as co-producer since the start of the show's third season.
Deschanel, with Alyson Hannigan, Jaime King, Minka Kelly, Taryn Southern, and Katharine McPhee made a video slumber party featured on FunnyorDie.com to promote regular breast cancer screenings for the organization Stand Up 2 Cancer.