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At the age of 16, Powers began working in radio drama, before becoming a film actress in 1950.
Powers' first movie roles were in Outrage and Edge of Doom in 1950. That same year, Stanley Kramer signed Powers to star opposite Jose Ferrer in what may be her most-remembered role, as Roxane in Cyrano de Bergerac. She was nominated for a Golden Globe Award for her part in this movie.
While on a USO entertainment tour in Korea in 1951, she contracted a blood disease and nearly died. She was treated with chloromycetin, but a severe allergic reaction resulted in the loss of much of her bone marrow. Powers barely survived, and her recovery took nearly nine months.
She began working again in 1952, including the lead in Rose of Cimarron (1952) and co-starring roles in City Beneath the Sea (1953) and City That Never Sleeps (1953), although she was still taking medication.
Following her recovery, she appeared in Bengazi (1955) and B-movie westerns, such as Rage at Dawn (1955), The Storm Rider (1957), and Sierra Baron (1958), and science fiction films, among them The Unknown Terror (1957), The Colossus of New York (1958), Flight of the Lost Balloon (1961), and Doomsday Machine (1972). She also had large roles in Tammy and the Bachelor (1957) and Daddy's Gone A-Hunting (1969).
In 1957, she was cast in Man on the Prowl with James Best, Ted deCorsia, and Vivi Janiss.
She appeared in more than one hundred television series episodes, including Appointment with Adventure, Crossroads, Mr. Adams and Eve, The Restless Gun, Wagon Train, Bourbon Street Beat, The Rebel, Maverick (in an episode called "Dutchman's Gold" with Roger Moore), The Everglades, Bonanza, The Man from U.N.C.L.E. (The Virtue Affair), Mission: Impossible, Bewitched as Adrienne Sebastian and Mary Jane Nilesmunster, The Wild Wild West, The Silent Force, Cheyenne episodes "Alibi for the Scalped Man" (1960) and "Trouble Street" (1961), and the Wanted: Dead or Alive episode "Till Death do us Part" with Steve McQueen.
In 1962, she portrayed Loretta Opel, a woman with leprosy, in the episode "A Woman's Place" on CBS's Rawhide.
On CBS's Perry Mason courtroom drama, Powers made five appearances in the 1950s and '60s. She was cast as defendant Clair Allison in the 1959 episode "The Case of the Deadly Toy". She also played defendant June Sinclair in the 1960 episode "The Case of the Crying Cherub". Her most memorable role was as defendant Janet Brent, friend of Perry's secretary Della Street (Barbara Hale), in the 1962 episode "The Case of the Weary Watchdog". In 1964 she portrayed murderer Helen Bradshaw in "The Case of the Frightened Fisherman", and in 1966 she played murder victim Elaine Bayler in "The Case of the Scarlet Scandal".
Powers played the recurring character Mona during the final season of Hazel (1965–66).
In 1971, Powers was cast, along with Mike Farrell and June Lockhart, opposite Anthony Quinn in the first of the fifteen episodes of the NBC television series The Man and the City.
Powers narrated Follow the Star, a Christmas album from RCA Victor.
Powers was a successful children's author of Follow the Star, Follow the Year, and Dial a Story. She also revised and edited two books by Enid Blyton after the author's death.