Scott was born Marlene Kringstad on January 26, 1943 in Robbinsdale, Minnesota. Initially upon coming to New York City she worked as a Playboy bunny and changed her name to Kathryn Leigh Scott. In 1966, she was cast as Maggie Evans the waitress-turned-governess on the ABC-TV cult serial Dark Shadows. During her tenure at the show, she played Josette du Pres Collins (a lover of Barnabas Collins (Jonathan Frid) who was killed at Widow's Hill in 1795), Rachel Drummond (a governess during 1897), Kitty Soames (aka Lady Hampshire on the second-half of the 1897 storyline), and Maggie Collins (Maggie Evans, who married Quentin Collins (David Selby) in Parallel Time 1970).

She appeared in House of Dark Shadows, a MGM picture based on the Dark Shadows TV series in 1970. That same year in September, she decided to leave the show to move to France with her boyfriend and photographer Ben Martin, whom she later married. A few months later, Dark Shadows ended its five year run in April 1971.

After Dark Shadows she made guest appearances on TV shows like Police Squad!, Quincy, Magnum, P.I., Cagney and Lacey (in which her Dark Shadows co-star John Karlen played Harvey Lacey, the husband of Mary Beth Lacey (Tyne Daly), Matlock, The Incredible Hulk, The A-Team, and The Next Generation. Also she appeared in movies like The Great Gatsby.

In 1979, she co-starred in the short-lived CBS series Big Shamus, Little Shamus with Brian Dennehy. In 1983, she co-starred in Philip Marlowe, Private Eye with Powers Boothe on HBO until 1986.

In 1986, just a year after her Dark Shadows co-stars Grayson Hall and Joel Crothers died, she founded a publishing company called Pomegranate Press in which she wrote books about Dark Shadows and other stories.

Today, she appears in yearly Dark Shadows Festivals, book signings, and other events. She later divorced Ben Martin, though the two remain business partners, and is now married to Geoff Miller. More recently, she has reprised a number of her Dark Shadows roles in a series of audio dramas.

She appeared in VH1's When Ruled the World series in episode called When Playboy Ruled The World, in which she was interviewed. She also appeared in the 2008 film Parasomnia.