Born Margaret Mary Emily Anne Hyra, on November 19, 1961, in Fairfield, Connecticut. Her mother, Susan, left the family when Ryan was 15 to become an actress; her father, Harry, a high school teacher, was left to raise the couple’s four children. After graduating from high school, she attended New York University, where she studied journalism and supported herself by appearing in commercials. She obtained a Screen Actor’s Guild card under her mother’s maiden name, Ryan, and made a successful film debut in Rich and Famous, directed by George Cukor and starring Candice Bergen; Ryan played the daughter of Bergen’s character. Ryan left college before finishing her degree and began acting on television, appearing in a 1982 ABC Afterschool Special entitled "Amy and the Angel" before landing a regular stint on the CBS daytime soap opera As the World Turns (1982-1984). In 1985, she moved to Los Angeles; her first substantial film role was in the hit film Top Gun (1986), starring Tom Cruise.

Her breakthrough role came in 1989, when she starred opposite Billy Crystal in the smart romantic comedy When Harry Met Sally. Ryan’s performance in that hit movie included a much-talked-about scene in a delicatessen in which she demonstrates for Crystal how easy it is for a woman to fake an orgasm; the scene has since been referred to as one of the great comic moments in film history.

If When Harry Met Sally was the film that first established her undeniable appeal as a leading actress in romantic comedies, Sleepless in Seattle (1993) was the one that cemented Ryan’s status as “America’s Sweetheart.” The winsome but predictable hit was her second collaborative effort with Tom Hanks—1990’s Joe Versus the Volcano was a flop—as well as with writer-director Nora Ephron, who also penned When Harry Met Sally. Five years later, the team of Ryan, Hanks, and Ephron scored again with You’ve Got Mail, a late-1990s update of the 1940 film Shop Around the Corner. Ryan’s other notable romantic comedies include Prelude to a Kiss (1992), co-starring Alec Baldwin; I.Q. (1994), co-starring Tim Robbins and Walter Matthau; and French Kiss (1995), co-starring Kevin Kline. The last film was the first release from Ryan’s Fox-based production company, Prufrock Pictures.

Ryan has generally had less success with her dramatic films, although she has displayed a considerable range stretching far beyond the perky persona showcased in her biggest hits. In 1990, she won acclaim for her portrayal of Jim Morrison’s drugged-out mistress in Oliver Stone’s The Doors (1991), starring Val Kilmer; she also turned in an emotionally-charged performance as a woman struggling with alcoholism in When a Man Loves a Woman (1994), co-starring Andy Garcia. Other more serious films for Ryan included the period comedy Restoration (1995); Courage Under Fire (1996), a military drama co-starring Denzel Washington; the black comedy Addicted to Love (1997), co-starring Matthew Broderick; City of Angels (1998), with Nicolas Cage; and the little-seen ensemble drama Hurlyburly, starring Sean Penn and Kevin Spacey. She also lent her famous voice to the title character in the 1997 animated feature Anastasia, about the lost daughter of the murdered Russian royal family.

In 2000, Ryan returned to the lightweight romantic comedy genre with Hanging Up, a film written by Ephron’s sister Delia, directed by Diane Keaton, and co-starring Keaton, Lisa Kudrow, and Matthau. In the romance/adventure, Proof of Life, released in December of 2000, she starred as the wife of an American kidnapped by South American terrorists, who turns to a hostage negotiator, played by Russell Crowe, for help.

While filming the critically panned comedy Innerspace (1987), Ryan fell in love with her co-star, Dennis Quaid. The couple appeared in two more films together, D.O.A. (1988) and Flesh and Bone (1993); both films met with little success. Ryan and Quaid married in 1991 (after Quaid underwent a highly publicized rehabilitation from his addiction to cocaine) and have one son, Jack Henry. The couple, who have homes in California and Montana, announced their separation in June 2000. At the same time, Ryan became romantically involved and was linked in the press to Crowe, her costar in the upcoming Proof of Life. Citing "irreconcilable differences" (and claiming there was no third party involved), Quaid filed for divorce in July, 2000. Ryan and Crowe split in late December of that year. The Quaid-Ryan divorce was finalized in July, 2001, but the couple remain friends and have joint custody of their son.

Biography courtesy of Biography.com.