After graduating from college, Ryan worked at MTV in its special effects department. She started acting in commercials while studying acting and improvisation in New York City. Since someone called Susan Ryan was already registered with the Screen Actors Guild, Ryan used her middle name instead. In 2000, she appeared in an episode of Sex and the City. She was in the Broken Lizard films Super Troopers and Beerfest, as well as Big Helium Dog and several independent films. Ryan’s most notable film role was in the 2003 film Open Water, for which she won the 2004 Saturn Award for Best Actress. Despite the film’s success, she made only one film in the next five years (Beerfest). She appeared in four films in 2008 and two in 2009, including Under New Management and It’s Complicated.