Barone was born in St. Louis, Missouri. She earned her BFA from the University of Detroit in 1986, followed by an MFA from Wayne State University, where she was taught by director/professor Robert T. Hazzard.
Barone appeared in the fourth-season Seinfeld episode "The Shoes" as Gail Cunningham, a chef who wants Elaine Benes' shoes. In the early 1990s, she was a regular cast member of Carol & Company with actress Carol Burnett. Barone also played Carol Willick, Ross Geller's ex-wife, in the character's first appearance in Friends. She left the show as she wanted to pursue a more full-time role and was replaced by Jane Sibbett. She starred on The Jeff Foxworthy Show for the first season (1995–1996) and in The War at Home from 2005 to 2007. In 2000, Barone also co-starred in the sitcom Daddio.
Barone's other television credits include Curb Your Enthusiasm, Quantum Leap, Empty Nest, Chicago Hope, Castle, Do Not Disturb, Ally McBeal, Caroline in the City, Party of Five and The Larry Sanders Show.

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