Ryan began her acting career in 1981 in minor roles, before joining the cast of the CBS soap opera As the World Turns in 1982.
Subsequently, she began to appear in supporting roles in films during the mid-1980s, achieving recognition in independent films such as Promised Land (1988) before her performance in the Rob Reiner-directed romantic comedy When Harry Met Sally...
Also starring Keaton, Lisa Kudrow, and Walter Matthau, the film adaptation of Delia Ephron's 1995 novel received poor reviews from critics.
She studied journalism as an undergraduate, first at the University of Connecticut and then at New York University.
During college, she acted in television commercials and the soap opera As the World Turns to earn extra money.
Around that same time, she appeared in a Burger King commercial.
Several television films and smaller film roles followed, including appearances in Charles in Charge, Armed and Dangerous, Amityville 3-D and Promised Land; for her role in the lattermost she received her first Independent Spirit Award nomination. Her first leading role was the romantic comedy film When Harry Met Sally...
(1989) brought her widespread attention and her first Golden Globe nomination.
Ryan subsequently established herself, both nationally and internationally, as one of the most successful actresses in the 1990s and early 2000s, particularly in romantic comedy films such as Sleepless in Seattle (1993), French Kiss (1995), You've Got Mail (1998), and Kate & Leopold (2001).
The same year, Ryan returned to type, starring alongside Tim Robbins in Fred Schepisi's romantic comedy I. The film centers on a mechanic and a Princeton doctoral candidate who fall in love, with the aid of the graduate student's uncle, Albert Einstein (played by Walter Matthau).
Also in 1994, Ryan won Harvard's Hasty Pudding Woman of the Year award, and People Magazine dubbed her one of "the 50 most beautiful people in the world".
In the film, she portrayed the distraught wife of a kidnapped engineer, played by David Morse, while relying on a resourceful troubleshooter who makes a profession of dealing with international bandits.
While the film became a lukewarm critical and commercial success, grossing million worldwide, it garnered much reportage in the tabloid press in association with Ryan and Crowe's affair.
Her other films include The Doors (1991), When a Man Loves a Woman (1994), Courage Under Fire (1996), Addicted to Love (1997), City of Angels (1998), Proof of Life (2000), and The Women (2008). She has two sisters, Dana and Annie, and a brother, musician Andrew Hyra, a member of the band Billy Pilgrim.