Deschanel was born as Mary Josephine Weir. Her ancestry includes Irish, French, Swiss, Dutch, and English. In her first major appearance in show Business in 1983, Deschanel played Annie Glenn, the wife of the Astronaut John Glenn (played by Ed Harris), in the movie adaptation of the Tom Wolfe book The Right Stuff.
Deschanel was featured a second time as the wife of a character played by Ed Harris, in the movie Winter Passing (2005), although she was only seen in a photograph on the wall. Despite never physically appearing in this movie, she did receive full billing in the credits as the character "Mary".
The next year, Deschanel played Betty Fernandez, the remarried former wife of the Astronaut Dave Bowman (played by Keir Dullea), in the film 2010. She also played the role of Mrs. Howard in the 2000 film The Patriot.