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 brought up 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.

McCormack's first notable role was as the character Murron 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.