Although she is best known for her work in TV, Powers did have an active feature film career in the 1960s. She failed one of her first auditions--as a dancer for the chorus of the film version of "West Side Story"--but was seen on that audition by another director and was cast in "Tammy, Tell Me True" (1961). She went on to star or co-star in "The Interns" (1962) and its 1964 sequel "The New Interns," "McClintock!" (1963) and numerous others, including "The Boatniks" (1970) and "Herbie Rides Again" (1974). But Powers first became an audience favorite as April Dancer on the 1966 NBC series "The Girl From U.N.C.L.E." fighting the world subversive T.H.R.U.S.H. organization. While the show did not last more than a year, the actress was set as far as TV audiences were concerned. As TV-movies became a weekly genre in the early 70s, Powers became one of their more popular stars with such fare as "Five Desperate Women" (ABC, 1971), and "Paper Man" (CBS, 1971) and then averaging three per season for the next few years. Some of her more memorable were "Hardcase" (ABC, 1972), in which she was a wife who ran off with a Mexican revolutionary in the Old West, and "Manhunter" (CBS, 1974) in which Powers played a Bonnie Parker type character hunted down by Ken Howard. Her next series effort, the short-lived "The Feather and Father Gang" (ABC, 1977), found her cast as an attorney with an ex-con parent (Harold Gould). Powers went on to play a featured role in the Watergate-inspired miniseries "Washington: Behind Closed Doors" (ABC, 1977), based on the John Ehrlichman novel. She also played non-fiction author Joan Barthel in the highly praised docudrama "A Death in Canaan" (CBS, 1978), about a Connecticut town that rallies around a teenager accused of murder.

In 1979, Powers landed what was to become her signature role, Jennifer Hart, journalist-turned-sleuth in "Hart to Hart." The chemistry between Powers and her co-star Robert Wagner was palpable and their portrayals of an 80s version of Nick and Nora Charles delighted audiences and helped make ABC the top rated network for several seasons. When the show folded in 1984, Powers became far more selective in her choices of TV work and spent more and more time in Kenya and elsewhere working to secure the future for wildlife. But she did return stateside when TV roles were of interest. She was mother to Melissa Gilbert and daughter to Maureen Stapleton and full of surprises in "Family Secrets" (1984), which also marked her producing debut. Other notable credits from this period include screenwriter Montana Gray, the most respectable of a rather mangy lot, in the highly-rated "Hollywood Wives" (ABC, 1985). In 1987, Powers won the applause of critics and the audience alike with her turn as Frances Schreuder, the high-strung mother who sends her sons off her to kill her father, in the based on fact "At Mother's Request" (CBS). By 1988, Powers was producing much of what she starred in, including "Beryl Markham: A Shadow of the Sun" (CBS). The role of pioneering adventurer Markham seemed tailor-made for Powers' real-life, reflecting her love of Africa. She and Wagner reprised their roles in "Hart to Hart: The Return" (NBC, 1993) and the pairing proved popular enough that at least two TV-movies were produced in each of the three succeeding seasons.

Powers' rapport and chemistry with Robert Wagner spilled over to the theater as well; the duo starred in a London production of A.R. Gurney's "Love Letters." The actress had honed her craft onstage previously in such musicals as "Oliver" and "Annie, Get Your Gun." In 1991, she made her West End debut in the London production of the musical "Matador," portraying a character loosely based on Ava Gardner, although the end result less than thrilled audiences and critics. In 1996, Powers stepped into the role of Margo Channing (created on film by Bette Davis and on stage by Lauren Bacall) in a pre-Broadway tour of the 1970 award-winning musical "Applause."

From 1964 to 1971, Powers was married to actor Gary Lockwood. For most of the 70s until his 1981 death, she was romantically involved with actor William Holden. Loyal to his memory, she has served as president of The William Holden Wildlife Education Center in Kenya, and participated in the 1989 bio-documentary "William Holden: The Golden Boy," which aired on the Arts & Entertainment Channel.