She gained popular acclaim for her first leading role as Kate Austen in the ABC series Lost (2004–10), which garnered her a nomination for the Golden Globe Award for Best Actress in a Drama Series and won her a Screen Actors Guild Award.
In 2008, Lilly starred as Connie James in the Academy Award winning war film The Hurt Locker (2008) and followed it with a role in the science fiction film Real Steel (2011).
She was raised in British Columbia by her mother, a produce manager and her father, a home economics teacher. She took the agent's business card but did not immediately pursue acting.
She eventually called and the agency landed her several roles in commercials and non-speaking parts in the TV shows Smallville and Kingdom Hospital.
Around 75 women auditioned for the part of Kate Austen.