O’Rourke was born in San Diego, California to Kathleen and Michael O’Rourke. Her mother worked as a seamstress and her father was a construction worker. She had an older sister, Tammy. Kathleen and Michael divorced in 1981, and O’Rourke’s mother married truck driver James A. “Jim” Peele in 1984. After her parents’ divorce, O’Rourke rarely saw her birth father and called her stepfather “Dad”.  Before O’Rourke began acting, the family lived in a trailer park in Anaheim. Her success later allowed the family to purchase a home in Big Bear Lake, California. In between acting jobs, O’Rourke attended Big Bear Elementary School where she was president of her class. At the time of her death, the family was living in Lakeside, California.

In a contemporary interview with American Premiere magazine, director Steven Spielberg explained that he was looking for a “‘beatific’ four-year-old child…every mother’s dream” for the lead in his 1982 horror film Poltergeist. While eating in the MGM commissary, Spielberg saw five-year-old Heather O’Rourke having lunch with her mother while older sister Tammy was shooting Pennies from Heaven. After his lunch, Spielberg approached the family and offered O’Rourke the Poltergeist role; she was signed the next day, beating Drew Barrymore who was up for the role.

In the Poltergeist trilogy, O’Rourke played Carol Anne Freeling, a young suburban girl who becomes the conduit and target for supernatural entities. The New York Times noted that she had played the key role in the films and commented, “With her wide eyes, long blonde hair and soft voice, she was so striking that the sequel played off her presence.” During the production of the original Poltergeist, Spielberg twice accommodated the child actress when frightened. When scared by performing a particular stunt, Spielberg replaced O’Rourke with a stunt double wearing a blonde wig; and when disturbed by the portrayal of adult abuse toward the child characters, Spielberg did not require her to perform the take again. For her work in Poltergeist, O’Rourke earned between US$35,000–$100,000. O’Rourke played the role in all three films. O’Rourke and Zelda Rubinstein were the only original cast members to appear in the third film, Poltergeist III.

O’Rourke’s delivery of the lines “They’re here!” in the first film, and “They’re baa-aack!” in the second (that film’s tagline), placed her in the collective pop culture consciousness of the United States. “They’re here!” is #69 on the American Film Institute’s list of 100 Movie Quotes.  After her work in 1982’s Poltergeist, O’Rourke secured several television and TV movie roles. In April 1983 she starred as herself alongside Morey Amsterdam and well-known Walt Disney animated characters in the hour-long television special, Believe You Can … and You Can! She also appeared in CHiPs, Webster, The New Leave It to Beaver, Our House, and had a recurring role on Happy Days as Heather Pfister. In the television movies Massarati and the Brain and 1985’s Surviving: A Family in Crisis, she played Skye Henry and Sarah Brogan, respectively.

O’Rourke became ill in early 1987 and was misdiagnosed by doctors at Kaiser Permanente Hospital as having Crohn’s disease. She was prescribed cortisone to treat the disease, which reportedly caused her cheeks to appear puffy and large. On January 31, 1988, O’Rourke suddenly became ill again, vomiting and unable to keep anything down. The next morning she collapsed while preparing to leave for the hospital and her stepfather called paramedics. O’Rourke suffered a cardiac arrest en route to the hospital, and after resuscitation she was airlifted by helicopter to Rady Children’s Hospital in San Diego,[10] where she died later that day.

Speaking to reporters, O’Rourke’s manager David Wardlow initially announced that it was believed she died of influenza. However, hospital spokesman Vincent Bond announced that O’Rourke died during surgery to repair an acute bowel obstruction (caused by congenital stenosis of the intestine) complicated by septic shock; this report was corroborated by the San Diego County coroner’s office on February 3, two days after her death. Later reports changed the specific cause of death to cardiac arrest caused by septic shock brought on by the intestinal stenosis.  O’Rourke was interred at Westwood Village Memorial Park Cemetery on February 5, 1988. Her tomb is a scheduled stop for “Haunted Hollywood” tours.