McCormack was born in Alton, Hampshire, England. She has Irish ancestry, as one of her grandfathers was Irish. Her mother died of lupus when McCormack was six years old, and her steelworker father subsequently raised her and her brother Stephen. She was brought up in the Catholic religion (though is now a "lapsed Catholic") and attended Convent of Our Lady of Providence. She then went on to study at the Oxford School of Drama.

McCormack's first notable role was as the character Murron MacClannough in the multiple Academy Award winning movie Braveheart. Her screen debut however was as the lead in the Anna Campion directed film Loaded, and has subsequently stated that she had a "miserable time with the director (Anna Campion)... it was my first film job, I needed to be mollycoddled, I needed to be helped through it, and I wasn't. Mostly, it was a horrible experience." After Braveheart, McCormack had lead roles in Nils Gaup's Northstar and Marshall Herskovitz's Dangerous Beauty. Other films include Spy Game and 28 Weeks Later. Despite being in demand, she does few films, stating that "I read very few scripts I'm passionate about... Maybe one in every twenty or thirty."

McCormack has shown preference in her career towards the theatre, saying that "theatre really is an actor's medium: you're on stage with no director anymore, whereas in film very rarely do you get much rehearsal other than running through the scene very quickly. Then everyone comes in and shoots it." McCormack was one of the original 2006 London cast of Patrick Barlow's play of The 39 Steps. In 2008, she performed the role of Nora in A Doll's House, directed by Peter Hall at the Theatre Royal, Bath, and also the role of Isabel Archer in a stage adaptation of The Portrait of a Lady, both of which commenced their runs in July 2008, ending in August, before transferring to the Rose Theatre in Kingston later that year.

In 2009 she will appear in the UK tour of Headlong's adaptation of Six Characters in Search of an Author.