Cole was born in Torquay, southwest England, and raised in London, along with one of her two sisters. She was raised by her mother, Patience Owen, an artist and writer; her father, Chris Cole, a boat builder and fisherman, left the household and was not part of his daughter's life while she grew up. Cole attended the St Marylebone church school for girls, before completing her sixth form studies at Latymer Upper School, an independent school in Hammersmith, London. A chance encounter began her modelling career at the age of 14.
In April 2007, Cole first featured in the Sunday Times Rich List, which estimated her net worth at £6 million, ranking her as the 77th-richest young person in the United Kingdom. As of 2009, she is thought to have earned in excess of £11 million.
Despite her successful modelling career, Cole retains a commitment to her education, achieving A grades in her A-level examinations in English, Politics, Drama, History, and Philosophy and Ethics at Latymer Upper School. Before Latymer School, Cole attended the primary school Hallfield School (Bayswater, London) and St Marylebone Secondary School.
Cole gained a place to read Social and Political Sciences at King's College, Cambridge, but twice deferred entry before switching to study History of Art, which she commenced in the Michaelmas term, 2008, gaining a First in her examinations at the end of her first year, and again in her second year examinations, one of seven members of her year to achieve the grade. Asked about the change of course, Cole explained, "I like doing things I haven't learnt about yet. I've always been interested in art, and I love doing art." Speaking to Judy Rumbold of The Irish Independent. she said, "the decision came from the vague notion that it might be a wise thing to do, that when I was 50, 60, 70, I'd look back and be glad I did it". She gave an interview for The Daily Telegraph in December 2009 in which she admitted she struggled to settle in to her first year at Cambridge, conceding she was "a bit shell-shocked, but I think everyone finds that".
Cole was in a relationship with American actor Enrique Murciano, star of television series Without a Trace. As of February 2011, the pair are reported to have broken up after two and half years of dating.
In an interview given in January 2010, Cole admitted, "I definitely never thought of myself as model material. Me on a catwalk with all these superwomen?" adding that "if a designer says I inspire them, I'm still not sure how that happened". Cole went on to reveal that her modelling career gave her "a lot of self confidence, which I didn’t have in the past". In February 2010, Cole was voted the fourth "sexiest redhead of all time", after Florence Welch, Prince Harry of Wales, and Nicola Roberts in a poll conducted by the Daily Mirror.
Cole's distinctive red hair has attracted significant media attention. She is also recognised for what Entertainment magazine described as her porcelain doll-like beauty.
Cole's modelling career was sparked from a chance encounter while walking through Soho when she was approached by Benjamin Hart, who asked her to consider modelling. She initially declined, later saying, "I was cynical enough to think it wouldn't come to much", though she later changed her mind and signed to Storm Models.
Her break came in 2003 when she caught the eye of photographer Steven Meisel. It was on that photoshoot, her first "only girl" story for Italian Vogue, that Cole was "catapulted into the spotlight" as one of the leading new faces of the year. Since then, Cole has worked with many other prominent photographers, including Craig McDean, Nick Knight, Juergen Teller, Arthur Elgort, and Irving Penn.
At the 2004 British Fashion Awards, Cole was named "Model of the Year". She has since made appearances on the covers of many fashion magazines including, amongst others, the American, Italian, British, Japanese and Korean editions of Vogue, Citizen K, V and Vogue as well as featuring on Vogue's "best dressed" list in December 2005. She has also had cover appearances on Numéro and Interview.
She has modelled on the international runway circuit and at many fashion shows on behalf of Chanel, Shiatzy Chen, DKNY, Jean Paul Gaultier, Versace, Alexander McQueen, Jasper Conran, John Galliano, and Louis Vuitton. She was nominated, for the second time, for the "Model of the Year" award at the 2007 British Fashion Awards and, in December 2009, was listed by Vogue Paris as one of the top 30 models of the 2000s.
Cole's modelling career continued in 2010. She made a cover appearance on the January 2010 issue of the Canadian Elle, as well as giving an interview to the magazine and opening Hermès's winter 2010/2011 collection at Paris Fashion Week in March, wearing a black leather catsuit and bowler hat.
Towards the end of 2010, she featured in a documentary chronicling the career of Rolf Harris in which he painted her dressing up as the Queen of the fairies from A Midsummer's Night Dream.