Byrne was cast in her first film role, Dallas Doll, when she was 12 years old. She has appeared in a variety of Australian television shows including Heartbreak High, Echo Point, and the film Two Hands alongside Heath Ledger. She appeared in The Date, My Mother Frank, and Clara Law's The Goddess of 1967 for which she obtained the Female Volpi Cup at the 2000 Venice Film Festival. Meanwhile, she appeared as a guest in an episode of the cop drama series Murder Call. She also acted on stage, playing a lead role in La Dispute and starred in a production of Anton Chekhov's classic Three Sisters at the Sydney Theatre Company.

Byrne appeared in the music video of Darren Hayes's single I Miss You and starred with Australian musician Alex Lloyd in the music video for his single Black The Sun and was featured on the cover artwork for the EP. She also appeared in the TV Commercial for Sony and reunited with Alex Lloyd, appearing in his music video for 1000 Miles from the album Distant Li