Cartwright began her career as a child actor in 1958 with a role in In Love and War. Among her early appearances was a semi-regular part in the television series Leave it to Beaver (1959) and an episode of The Twilight Zone titled "I Sing the Body Electric" (1962). She appeared in the films, The Children's Hour (1961) and Alfred Hitchcock's The Birds (1963) which were both very successful, and she was a regular on the television series Daniel Boone from 1964 until 1966, however Cartwright's career slowed down during the 1960s. She continued to work sporadically and achieved two of her biggest successes with Invasion of the Body Snatchers (1978) and Alien (1979).

Her other film roles include Spencer's Mountain (1963), Inserts (1976), Goin' South (1978), The Right Stuff (1983), Flight of the Navigator (1986), The Witches of Eastwick (1987), Shoot the Moon (1996), Money Talks (1997), Scary Movie 2 (2001), Kinsey (2004), and Straight-Jacket (2004).

A frequent performer on television, she has played guest roles in such series as The Mod Squad, Miami Vice, Baywatch, L.A. Law, ER, The X-Files, Chicago Hope, Will & Grace, Touched by an Angel, Judging Amy and Six Feet Under.

Cartwright has received three Emmy Award nominations, one for her work in ER in 1997, and two for her work on The X-Files in 1998 and 1999.

She is the sister of the actress Angela Cartwright, who appeared in The Sound of Music (1965) and in the television series Lost In Space. She will co-star in her second remake of Invasion of the Body Snatchers, following the 1978 version directed by Philip Kaufman.