Born in Manhattan to actress Tippi Hedren, she was raised mainly in Los Angeles, where she graduated from the Hollywood Professional School at age 16.

Griffith's subsequent performance in the comedy Something Wild (1986) attracted critical acclaim before she was cast in 1988's Working Girl, which earned her a nomination for the Academy Award for Best Actress and won her a Golden Globe.

Other credits include John Schlesinger's Pacific Heights (1990), Milk Money (1994), the neo-noir film Mulholland Falls (1996), as Charlotte Haze in Adrian Lyne's Lolita (1997), and Another Day in Paradise (1998).

She played the voice of Margalo in Stuart Little 2 (2002), and later starred as Barbara Marx in The Night We Called It a Day (2003), and spent the majority of the 2000s appearing on such television series as Nip/Tuck, Raising Hope, and Hawaii Five-0.

[5] During her childhood and adolescent years, she lived part of the time in New York with her father and part-time in Antelope Valley, California, where her mother formed the animal preserve Shambala.

A contemporaneous profile of Griffith in Newsweek addressed her image at the time, in which it was noted: "She has the body of a sensuous woman, the pouting, chipmunk face of a teenager, and the voice of a child–and, suddenly, she's showing them all.

[14] In 1977, she had a supporting part playing a hitchhiker in the Lamont Johnson-directed sports drama One on One,[15] where John Simon in his review of One on One wrote, "Griffith is miscast in a PG picture, where she is obliged to hide her one talent (or two depending on how you count it...them)".

[16] Griffith appeared in the Israeli experimental film The Garden, in which she portrayed a naked mute woman in Jerusalem whom a man mistakes for an angel.

[17] The same year, she had a supporting role in Joyride opposite Robert Carradine, in which she played a young woman who leaves California with her boyfriend, hoping to start a fishing company in Alaska.

[15] Griffith's well-known drug and alcohol addictions temporarily stalled her career in the early 1980s,[20] but she made a comeback at age 26 with her role as a pornographic film actor in the Brian De Palma thriller Body Double (1984).

[21] She then appeared in a supporting role in Abel Ferrara's thriller Fear City (1985), playing a stripper and prostitute in Times Square being stalked by a serial killer.

The following year, she had her first starring role opposite Jeff Daniels in Jonathan Demme's comedy Something Wild (1986), playing a mysterious woman who becomes involved with a straightlaced banker on a chance meeting.

[23] Critic Roger Ebert wrote of her acting: "Griffith's performance is based not so much on eroticism as on recklessness: She is able to convince us (and Daniels) that she is capable of doing almost anything, especially if she thinks it might frighten him.

[26] She subsequently starred opposite Sean Bean, Tommy Lee Jones, and Sting in Mike Figgis's neo-noir Stormy Monday (1988), portraying an American woman who becomes embroiled in her ex-boss's plot to acquire a jazz club in Newcastle upon Tyne.

"[27] Griffith achieved mainstream success when Mike Nichols cast her as spunky secretary Tess McGill in the box-office hit Working Girl (1988), co-starring Harrison Ford, Sigourney Weaver, Alec Baldwin, and Joan Cusack.

[32] After her pregnancy, Griffith began filming the thriller Pacific Heights (1990), directed by John Schlesinger, in which she portrayed a woman, who along with her boyfriend, becomes embroiled in a dispute with a criminal boarder in their San Francisco home.

Peter Travers of Rolling Stone panned the film, noting that it "achieves a consistency of ineptitude rare even in this era of over-inflated cinematic air bags...  Griffith has the curves and the Southern-belle voice of McCoy's mistress, Maria Ruskin, but the script robs this magnolia of her steel.

"[35] She was then cast in a lead role in Paradise (1991), a remake of the 1987 French film The Grand Highway, opposite then-husband Don Johnson, Elijah Wood, and Thora Birch.

"[36] In 1992, she starred as Linda Voss, a German Jewish secretary in Berlin, opposite Michael Douglas in Shining Through, a World War II-set drama based on the 1988 novel of the same name.

Billie Dawn is a naive, uneducated showgirl whose wealthy, powerful and crude long-term fiancé (John Goodman) hires a reporter (Don Johnson) to give her enough polish to make her presentable as his wife in Washington, D.C.[41] "This is supposed to be snappy material, and it comes across gloomy", Roger Ebert wrote at the time.

Among the few genuinely amusing scenes here are those that show her flouncing through the small town where Frank and Dad live, scandalizing the locals and even finding one ex-client strolling with his wife on Main Street.

[43] In the film, Griffith portrays the wife of a contractor (Willis) who has disputes with a free-spirited older man (Newman) in an upstate New York town.

In the midst of her separation, she appeared in an ensemble cast in the coming-of-age drama Now and Then, playing an actress who returns to her Indiana hometown to reunite with her childhood friends.

[56] She followed this with a starring role as a free-spirited heroin addict in Larry Clark's independent film Another Day in Paradise, opposite James Woods.

In the film, Griffith played an eccentric woman in 1960s Alabama who kills her husband and heads to Hollywood to become a movie star; this plot is set against a subplot involving a race-related murder.

[62] In 1999, Griffith was cast as Honey Whitlock, an arrogant actress kidnapped by a gang of underground filmmakers, in John Waters's black comedy Cecil B.

[66] Derek Elley of Variety panned the film, referring to it as "a straight-to-vidbin stiff...  this wannabe romantic comedy is chock full of phony sentiment.

[67] While in treatment, Griffith began making public blog posts in an online journal detailing her battle to beat her substance abuse.

[75] Prior to Hawaii Five-0, Griffith's television work included the short-lived WB sitcom Twins (2005–06), and the 2007 series Viva Laughlin, which was canceled after two episodes.

[84] In 2017, Griffith costarred opposite Al Pacino and Evan Peters in The Pirates of Somalia (originally titled Where the White Man Runs Away),[85] a biopic about journalist Jay Bahadur;[85] and played Jean Shelton in James Franco's The Disaster Artist, a comedy based on Greg Sestero's book of the same name.