After starring opposite Humphrey Bogart in In a Lonely Place (1950), she achieved her highest profile with Sudden Fear (1952), The Big Heat (1953), Human Desire (1954), and Oklahoma!

[7] An early stage appearance was in the long-running farce Good Night, Ladies at Chicago's Blackstone Theatre, starring Buddy Ebsen, which opened on April 12, 1942.

[8] Grahame made her Broadway debut on December 6, 1943, at the Royale Theatre as Florrie in Nunnally Johnson's The World's Full of Girls, which was adapted from Thomas Bell's 1943 novel Till I Come Back to You.

[10] She made her film debut in Blonde Fever (1944) and then achieved one of her most widely praised roles as the vixenish Violet Bick, saved from disgrace by George Bailey in It's a Wonderful Life (1946).

[11] Grahame starred with Humphrey Bogart in the film In a Lonely Place (1950) for Columbia Pictures, a performance for which she gained praise.

Though today it is considered among her finest performances, it was not a box-office hit, and Howard Hughes, owner of RKO, admitted that he never saw it.

[12] Grahame's other memorable roles included the scheming Irene Neves in Sudden Fear (also 1952); mob moll Debby Marsh in Fritz Lang's The Big Heat (1953) in which, in a horrifying off-screen scene, she is scarred by hot coffee thrown in her face by Lee Marvin's character; and the femme fatale Vicki Buckley in Fritz Lang's Human Desire (1954).

Grahame appeared as wealthy seductress Harriet Lang in Stanley Kramer's Not as a Stranger (1955) starring Olivia de Havilland, Robert Mitchum, and Frank Sinatra.

Grahame also did her own stunts as Angel the Elephant Girl in Cecil B. DeMille's The Greatest Show on Earth, which won the Oscar for best film of 1952.

She, whom audiences were used to seeing as a film noir siren, was viewed by some critics to be miscast as an ignorant country lass in a wholesome musical, and the paralysis of her upper lip from plastic surgery altered her speech and appearance.

[12] The play The Time of Your Life was revived on March 17, 1972, at the Huntington Hartford Theater in Los Angeles with Grahame, Henry Fonda, Richard Dreyfuss, Lewis J. Stadlen, Ron Thompson, Jane Alexander, Richard X. Slattery, and Pepper Martin among the cast, and Edwin Sherin directing.

[17] Over time, Grahame became increasingly concerned with her physical appearance; she particularly felt her upper lip was too thin and had ridges that were too deep.

According to her niece, Vicky Mitchum, Grahame's obsession with vanity led her to undergo more cosmetic procedures that rendered her upper lip immobile because of nerve damage.

After learning of her marriage to Anthony Ray, Grahame's third husband, Cy Howard, attempted to gain sole custody of the couple's daughter.

Turner authored a book about his time with Grahame called Film Stars Don't Die in Liverpool, which was later turned into a movie of the same name.

She underwent radiation treatment, changed her diet, stopped smoking and drinking alcohol, and sought homeopathic remedies.

In autumn 1981, while performing at The Dukes in Lancaster, England, Grahame fell ill.[33] She told her former lover, actor Peter Turner, and asked him not to contact doctors or her family (which he did anyway).

She was immediately admitted to St. Vincent's Hospital in Manhattan on October 5, 1981, where she died a few hours later of stomach cancer and peritonitis at age 57.

[37][38] On November 16, 2017, the motion picture Film Stars Don't Die in Liverpool (2017), based on Peter Turner's account of the final years of Grahame's life, was released in the United Kingdom.