Davis made her acting debut in the satirical romantic comedy Tootsie (1982) and starred in the science-fiction thriller The Fly (1986), one of her first box office hits.

While the fantasy comedy Beetlejuice (1988) brought her to prominence, the romantic drama The Accidental Tourist (1988) earned her the Academy Award for Best Supporting Actress.

However, Davis's roles in the box office failures Cutthroat Island (1995) and The Long Kiss Goodnight (1996), both directed by then-husband Renny Harlin, were followed by a lengthy break and downturn in her career.

She has portrayed the recurring role of Dr. Nicole Herman in Grey's Anatomy (2014–2015, 2018) and that of Regan MacNeil/Angela Rance in the first season of the horror television series The Exorcist (2017).

[5][6] She attended Wareham High School and was an exchange student in Sandviken, Sweden, where she became fluent in Swedish and got engaged to classmate Mats Dahlsköld, with whom she still corresponds by letter.

[10][11] Davis was working as a model when she was cast by director Sydney Pollack in his film Tootsie (1982) as a soap opera actor, whom she has described as "someone who's going to be in their underwear a lot of time".

[15] She next won the regular part of Wendy Killian in the television series Buffalo Bill, which aired from June 1983 to March 1984; and had a writing credit in one episode.

Davis concurrently guest-starred in Knight Rider, Riptide, Family Ties and Remington Steele, and followed with a series of her own, Sara, which lasted 13 episodes.

[17] They also starred in the sci-fi thriller The Fly (1986), loosely based on George Langelaan's 1957 short story of the same name, where Davis portrayed a science journalist and an eccentric scientist's love interest.

[19] Director Tim Burton cast Davis in his horror comedy Beetlejuice (1988)[20] as one of a recently deceased young couple who become ghosts haunting their former house; it also starred Alec Baldwin, Michael Keaton and Winona Ryder.

[21] Davis took on the role of an animal hospital employee and dog trainer with a sickly son in the romantic drama The Accidental Tourist (1988), alongside William Hurt and Kathleen Turner.

Critic Roger Ebert, who gave the film four stars out of four, wrote: "Davis, as Muriel, brings an unforced wackiness to her role in scenes like the one where she belts out a song while she's doing the dishes.

Despite modest box office returns,[23] the Chicago Tribune found the lead actors "funny and creative while keeping their characters life-size".

It reached number one at the box office, became the tenth highest-grossing film of the year in North America,[26] and earned Davis her first nomination for the Golden Globe Award for Best Actress in a Motion Picture – Musical or Comedy.

Although it flopped at the box office, Roger Ebert felt Davis was "bright and convincing as the reporter (her best line, after surviving the plane crash, is shouted through an ambulance door: "This is my story!

In her other 1994 release, the romantic comedy Speechless, Davis reunited with Michael Keaton to play insomniac writers who fall in love until they realize that both are writing speeches for rival candidates in a New Mexico election.

While The Long Kiss Goodnight managed to become a moderate success, Cutthroat Island flopped critically and commercially and was once listed as having the "largest box office loss" by Guinness World Records.

[36] Written by Brian Carbee and based on his own childhood and adolescence, the film received a limited theatrical release and mixed reviews from critics.

[39] She played the recurring role of Dr. Nicole Herman, an attending fetal surgeon with a life-threatening brain tumor, during the 11th season of Grey's Anatomy (2014–2015).

In the television series The Exorcist (2016), based on the 1973 film of the same name, Davis took on the role of grown-up Regan MacNeil, who has renamed herself Angela Rance to find peace and anonymity from her ordeal as a child.

In 2017, Davis starred in the film adaptation Marjorie Prime, alongside Jon Hamm, playing the daughter of an 85-year old experiencing the first symptoms of Alzheimer's disease,[41] and appeared as the imaginary god of a heavyset 13-year-old girl in the comedy Don't Talk to Irene.

[43] In 2018, Davis returned to Grey's Anatomy, reprising the role of Dr. Nicole Herman in the show's 14th season,[44] and executive produced the documentary This Changes Everything, in which she was also interviewed about her experiences in the industry.

[45] In 2019, she joined the voice cast of She-Ra and the Princesses of Power as Huntara,[46] and executive produced CBS educational show Mission Unstoppable through her organization.

[50] In October 2022, HarperOne published Davis's Dying of Politeness: A Memoir of her journey from childhood conventional New England femininity and trauma to feminist "badassery", one role at a time, on screen and in the real world.

Davis filed for divorce on August 26, 1997, a day after her personal assistant Tiffany Bowne[61] gave birth to a son fathered by Harlin.

[71] In 2005, Davis teamed up with the non-profit group Dads and Daughters to launch a venture dedicated to balancing the number of male and female characters in children's television and movie programming.

[76] In 2011, Davis became one of a handful of celebrities attached to USAID and Ad Council's FWD campaign, an awareness initiative tied to that year's East Africa drought.