Byrne was born in Balmain, a suburb of Sydney, Australia, of Irish and Scottish descent (her grandfather was an Irish immigrant to Australia). She is the daughter of Jane, a primary school administrator, and Robin Byrne, a semi-retired statistician and market researcher. She is the youngest of their four children; she has an older brother, George, and two older sisters, Alice and Lucy. Both of her parents are atheists, and she describes herself as agnostic. Byrne attended Balmain Public School and Hunters Hill High School before attending Bradfield Senior College in Crows Nest. She began taking acting classes at age eight, joining the Australian Theatre for Young People and later attended the University of Sydney. In 1999, Byrne studied acting at the Atlantic Theatre Company developed by David Mamet and William H. Macy.
In 2007, she played Cassie, the pilot in Danny Boyle's science fiction suspense film Sunshine, Scarlett Ross, an army medical officer in Juan Carlos Fresnadillo's science fiction horror 28 Weeks Later, the sequel to Boyle's 28 Days Later, and appeared in the independent film Just Buried, a Canadian dark comedy written and directed by Chaz Thorne.Since 2007, Byrne has appeared in the FX drama production Damages, playing the regular lead role of Ellen Parsons, a young attorney torn between her new boss, played by Glenn Close, and her own ambitions.
In 2009, Byrne co-starred with Nicolas Cage in the science fiction thriller, Knowing. Later that year, she appeared in the indie film, Adam, with Hugh Dancy. She appeared in the 2010 comedy film, Get Him to the Greek, starring Russell Brand and Jonah Hill and she was joint lead in the James Wan horror film Insidious, which premiered in September 2010 at the Toronto International Film Festival and went on general release on 1 April 2011.Byrne was the face of Max Factor between 2004 and 2006 and named in the Most Beautiful People of 2007 list in Who Magazine.
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