Beverly D'Angelo was born to musical parents; her mother played the violin and her father played the bass. She studied voice when she was young but soon abandoned it to become an actress. She first appeared on stage in 1975 performing in The Zinger, and then played Ophelia in a musical in New York City entitled Rockabye Hamlet.

Her acting career truly took off in the late 1970s, thanks to roles in huge films such as Annie Hall, Every Which Way But Loose and Coal Miner's Daughter. However, her biggest breakthrough came in 1983 when she first played the role of long-suffering but optimistic Ellen Griswold opposite Chevy Chase in National Lampoon's Vacation, a role she reprised three more times over the next 14 years, ending with 1997's Vegas Vacation. Along with many other films, she had a notable role in American History X with Edward Norton.

On television, Beverly D'Angelo has three times played recurring characters. The first role was as Lurleen Lumpkin on a 1992 episode of The Simpsons, which she reprised in 2008. She also played a defense attorney in a number of episodes of Law and Order: SVU. Finally, she has played Barbara ‘Babs' Miller, Ari Gold's mentor and business partner, on HBO's Entourage.