Born Monetta Eloyse Darnell in Dallas, Texas, and one of five children, Darnell was a model by the age of 11 and was acting in theater by the age of 13. She was chosen by a talent scout to go to Hollywood but was sent home to Dallas when the scout discovered she had lied about her age.

By 1939 Darnell had returned to Hollywood and immediately began to secure good roles, appearing in such films as Blood and Sand, Hangover Square and My Darling Clementine. She was cast uncredited as the Virgin Mary in The Song of Bernadette in 1943, in a controversial move by director Darryl F. Zanuck. In 1947 she won the starring role in the highly anticipated movie Forever Amber.

Publicity at the time suggested that Forever Amber would be the next Gone with the Wind, and the search for Amber, the title character of an amorous, upwardly mobile beauty in 17th-century England, was deliberately modelled on the extensive process that led to the casting of Scarlett O'Hara, but the film did not live up to its hype.

Darnell played two roles that earned her respect as an actress: as Daphne de Carter in the Preston Sturges comedy Unfaithfully Yours, opposite Rex Harrison, and as one of the three wives in contemporary wartime drama A Letter to Three Wives. Darnell's hard-edged performance in the latter won her the best reviews of her career. She was widely tipped to win an Academy Award nomination for this part, but, when this did not happen, her career began to wane, and her film appearances were sporadic thereafter. Further hampering Darnell's career was the actress's alcoholism and weight gain, which was attributed to both alcohol and overeating.

Darnell was married to cameraman J. Peverell Marley (1943-1952), brewery heir Philip Leibmann (1954-55), and pilot Merle Roy Robertson (1957-1963). Darnell and her first husband adopted a daughter, Charlotte Mildred "Lola" Marley, the actress's only child, who is the owner of The Smoking Lamp tobacco shop in Charleston, South Carolina.

Darnell died at the age of 41 on April 10, 1965, from the burns she received in a house fire in Glenview, Illinois, while staying with friends.

Her 1940 film, Star Dust, was playing on television the night of the fire, and Darnell fell asleep with a lit cigarette while watching it. She reportedly awoke and tried to save her friend's child in the house -- the young girl had already escaped -- and instead was burned over 80 percent of her body. She died the next day.

Her ashes are interred at the Union Hill Cemetery, Chester County, Pennsylvania, in the family plot of her son-in-law.

She has a star in Hollywood on the Hollywood Walk of Fame at 1631 Vine St.