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Smith was born in Paris, France, and raised in Washington, D.C., USA. She is the daughter (and namesake) of Joseph Yeardley "Joe" Smith (March 8, 1932–July 17, 2005), The Washington Post's first official obituary editor (1977–1988), who continued working full time for The Post until 1996. Her mother, Martha Mayor was a gallery worker. Her parents then later divorced.
In addition to performing as the voice of Lisa Simpson and other occasional characters on The Simpsons, Smith also appeared on the sitcoms Herman's Head and Dharma and Greg and guest-starred on Showtime's Dead Like Me, the Disney Channel's Phil of the Future, the "Mathnet" segment of the Children's Television Workshop show Square One and The Big Bang Theory. Smith co-starred on Herman's Head with Simpsons actor Hank Azaria. One notable line of hers on the show referred to her voice acting when she angrily answers a call with "I do not sound like that Lisa Simpson character on TV!"
Some of her film credits include The Legend of Billie Jean, Maximum Overdrive, City Slickers and As Good as It Gets.
Yeardley admitted on The Jane Pauley Show that she had struggled with bulimia for 25 years. Coincidentally, her character Lisa Simpson suffered through an eating disorder in the episode "Sleeping with the Enemy". She is currently performing in a one-woman show called More where she exposes her eating disorder. Yeardley has been cured of bulimia as of 2005.
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