After gaining minor roles in movies including Annie Hall, D'Angelo had a string of hit movies in the late 1970s, appearing in Every Which Way But Loose, Hair, and Coal Miner's Daughter (she portrayed the singer Patsy Cline, and did all her own singing). Her biggest break came with Chevy Chase in the 1983 National Lampoon film Vacation. Her role as Ellen Griswold was reprised in three Vacation sequels from 1985 through 1997. In 1992 Beverly had a guest appearance in the third season of The Simpsons as Lurleen Lumpkin, a singing waitress, in Colonel Homer.

After the end of her romance with film director Miloš Forman, in 1981, D'Angelo married Lorenzo Salviati, an economics student who also was an Italian duke; half-Polish, he is a descendant of Lorenzo de Medici. Separated in 1983, D'Angelo and Salviati finally divorced in 1995.

From 1985 until 1991, D'Angelo, although still married to the Duke, lived with Irish director Neil Jordan. During this time she had a small role in his 1988 comedy High Spirits, as well as the operatic film Aria (1987) in which she played Gilda in the Rigoletto scene (music by Verdi). Later she began a relationship with Anton Furst, an Academy award-winning production designer, who committed suicide in 1991 after they broke up.

In 1997, D'Angelo became involved with the actor Al Pacino. They are the parents of twins Olivia and Anton, who were born in 2001. The couple broke up soon after the children's birth and have battled over their custody ever since.

D'Angelo's father, Gene D'Angelo, was the longtime general manager for WBNS-TV, channel 10, the CBS affiliate in Columbus.