Darby's 1960s television roles included two appearances on the NBC series Mr. Novak, starring James Franciscus; she was cast as Julie Dean in "To Lodge and Dislodge" (1963) and as Judy Wheeler in "The Silent Dissuaders" (1965). Darby also appeared about this time on The Eleventh Hour, The Fugitive, The Donna Reed Show, Ironside, and in the first season of Star Trek as the title character in "Miri".

Darby began acting at age fifteen. Her first appearance was as a Dancer in the film Bye Bye Birdie (1963). Among her roles are True Grit, in which she played a fourteen-year-old when she was twenty-one years of age; Gunsmoke (1967 episodes "The Lure" and "Vengeance"); Bonanza (1967 episode "The Sure Thing"); The One and Only (1978); Better Off Dead (1985); and Halloween: The Curse of Michael Myers (1995).

Darby was cast in an episode of the NBC sitcom The John Forsythe Show ("'Tis Better Have Loved and Lost", 1965). and as Angel in the two-part Gunsmoke episode "Vengeance." She appeared in the episode "Faire Ladies of France" (1967) of the NBC western series The Road West starring Barry Sullivan and a Bonanza episode "A Sure Thing" (1967) as Trudy Loughlin, guest starring Tom Tully as Burt Loughlin, her father. She also appeared in 3 episodes of Gunsmoke: "The Lure" (1967) as Carrie Neely, "Vengeance: Part 1" (1967) as Angel, and "Vengeance: Part 2" (1967) again as Angel. She was cast in the 1972 movie, The People, which also starred william Shatner, reuniting them from their Star Trek appearance. She also played the unhinged Virginia Calderwood in the first television miniseries, Rich Man, Poor Man with Nick Nolte, Peter Strauss, and Susan Blakely in 1976.

Darby has been married twice. In 1968, she married James Stacy, with whom she had one child: Heather Elias (Stacy) (born 1968) Their marriage ended in divorce in 1969. In 1970, she married James Westmoreland; the marriage ended in divorce later that same year.

Darby admitted her career declined after the 1970s partly because she became an amphetamine addict. In 1990, she began to teach acting in the Los Angeles area and has been an instructor in the Extension Program at the University of California, Los Angeles since 1992. Darby also appeared as a female convict in an episode of The X-Files ("Sein und Zeit", 1999) who falsely confesses to the murder of her son who disappeared under mysterious circumstances that are being investigated by Fox Mulder and Dana Scully.

Darby also had the central role of Sally Farnham in the made-for-TV horror film Don't Be Afraid of the Dark (1973). Her subsequent television roles included guest appearances on Crazy Like a Fox, Family, The Love Boat, The Streets of San Francisco, Riptide, and Becker.

In 2014, she played Stacia Clairborne, a partially blind witness to a crime, in the episode "Prologue" of the show Perception.