Widely credited with the birth name of Stefania Zofia Federkiewicz, her California birth record lists her as Stefanie Zofya Paul.

As an actress, the red headed Powers appeared in several motion pictures in the early 1960s in secondary roles such as the 1962 comedy If a Man Answers with Sandra Dee and Bobby Darin and in 1963 in a serious role as the daughter of John Wayne in McLintock!. In 1966, her "tempestuous" good looks led to a starring role in the short-lived television spy thriller series, The Girl from U.N.C.L.E..

Although she continued to appear in television guest roles and made-for-TV films, she is best known for her role opposite Robert Wagner in the 1979-1984 hit television series, Hart to Hart for which she received two Emmy and five Golden Globe Award "best TV actress" nominations. In 1993 she won the Sarah Siddons Award for her stage performance in "Love Letters."

Married to actor Gary Lockwood between 1966 and 1972, she began a relationship with actor William Holden that led to their being involved with wildlife conservation. Following his death in 1981, Powers became President of the "William Holden Wildlife Foundation" and a director of the Mount Kenya Game Ranch in Kenya. In the United States, she works with both the Cincinnati and Atlanta zoos. She devotes a great deal of time to the cause and is international guest speaker on wildlife preservation.

On April 1, 1993 she married French aristocrat, Patrick de la Chesnais, but they divorced in 1999.

For her contribution to the television industry, Stefanie Powers has a star on the Hollywood Walk of Fame at 6778 Hollywood Blvd.

In 2003 she toured the UK in the singing role of Anna Leonowens in a revival of The King and I. She also toured the U.S. in 2004 and 2005 in her role as Leonowens.

Powers is one of many notable graduates from Hollywood High School, including classmate Nancy Sinatra.