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...
During college, she acted in television commercials and the soap opera As the World Turns to earn extra money.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.(This award is given to "outstanding women who, through their endurance and the excellence of their work, have helped to expand the role of women within the entertainment industry".) In 1996, Ryan starred in the film Courage under Fire alongside Denzel Washington and Matt Damon.
In 1997, Ryan voiced the lead role in the animated film Anastasia, which garnered good reviews and enjoyed box office success.
Around that same time, she appeared in a Burger King commercial.