She had her breakthrough starring as Carol Anne Freeling in the supernatural horror film Poltergeist (1982), which received critical acclaim and established her as an influential figure in the genre.

O'Rourke also worked in television, appearing in the recurring roles of Heather Pfister on the comedy series Happy Days (1982–1983) and Melanie in the sitcom Webster (1983), as well as starring as Sarah Brogan in the television-film Surviving: A Family in Crisis (1985).

On February 1, 1988, O'Rourke died following two cardiac arrests, her cause of death later being ruled as congenital stenosis of the intestine complicated by septic shock.

Her parents divorced in 1981, and O'Rourke's mother married part-time truck driver Jim Peele in 1984, while they were living in a trailer park in Anaheim, California.

[10] In a contemporary interview with American Premiere magazine, producer Steven Spielberg explained that he was looking for a "beatific four-year-old child...every mother's dream" for the lead in his horror film Poltergeist (1982).

[11][14] In Poltergeist, O'Rourke played Carol Anne Freeling, a young suburban girl who becomes the conduit and target for supernatural entities.

[29] En route, she suffered cardiac arrest, but paramedics were able to restart her heart at 9:25 a.m.[29] She was subsequently flown to the Children's Hospital of San Diego,[29] where it was discovered she had intestinal stenosis and went into emergency surgery.

[12][31][32] Daniel Hollander, the head of gastroenterology at the University of California, Irvine Medical Center stated that O'Rourke's death was "distinctly unusual" as she lacked prior symptoms of the bowel defect: "I would have expected a lot of [digestive] difficulties throughout her life and not just to have developed a problem all of a sudden.

[27] A private funeral was held for O'Rourke on February 5 in Los Angeles,[27] and she was entombed at Westwood Village Memorial Park Cemetery.