Scott made her motion picture debut in William Castle's Macabre (1958). During production of Macabre in 1957, she met Gene Lesser, and they were married a few months later.
She started her career in television by playing opposite such stars as Helen Hayes on live television. Between 1958 and 1960, Scott made three guest appearances on Perry Mason: Amelia Armitage in "The Case of the Daring Decoy" (1958), Sally Wilson in "The Case of the Glittering Goldfish" (1959), and Kathi Beecher in "The Case of the Violent Village" (1960).
In the television series The Fugitive, Scott played the sister of Dr. Richard Kimble (David Janssen) in four episodes telecast between 1964 and 1967, including the two-part finale that at the time became the highest-rated program in television history. Among other roles in "Have Gun - Will Travel," she played Stacy Neal (Season 2, Episode 16, The Wager). She also appeared as James Stewart's character's wife in the theatrical film Firecreek (1968) with Henry Fonda.
In July 2007, Scott was among celebrities at the Western Film Fair in Charlotte, North Carolina. Others in attendance were Lynn Borden, Brett Halsey, Rick Lenz, Betty Lynn, Joyce Meadows, and Lana Wood.
Jacqueline Scott died on July 23, 2020 at her home in Los Angeles from lung cancer.