Miller was born in New York City. She moved to England as a child and attended the Heathfield School in Ascot, Berkshire and later studied for a year at the Lee Strasberg Institute in New York City. Culturally, she considers herself English.

Miller's father, Edward Miller, is an American banker; and her mother Jo Miller, is a South African who ran Lee Strasberg's acting academy in London. Her parents parted when she was six years old; her father subsequently married (and later separated from) the English interior designer Kelly Hoppen. Miller has one sister, Savannah, who is a fashion designer; two half-brothers, Charles and Steven; and one former step-sister, Natasha (daughter of Hoppen).

Prior to her professional acting career, Miller worked as a photographic model. She currently models for Pepe Jeans, and she posed for Vanity Fair magazine's 2006 Hollywood Issue topless and smoking a cigarette.

She had a recurring role in the television series Keen Eddie. Miller appeared in supporting roles in the 2004 remake of the 1966 movie Alfie as well as in Layer Cake (2004). She played the female lead opposite Heath Ledger in the period drama, Casanova (2005).

In 2005, Miller made West End debut as Celia in Shakespeare's As You Like It to mixed reviews. (The Guardian commented "if she were in a girls' school show, rather than the West End, you would think her well above average.") She played the role of Rosalind for one performance, when Helen McCrory, the actress playing the lead, fell ill.

Miller has several high-profile projects due out in the next few years. She stars in the highly anticipated bio-pic of 1960s socialite and Andy Warhol's muse Edie Sedgwick in the film Factory Girl, set for a September 2006 release. In 2007, she stars opposite Michelle Pfeiffer and Robert DeNiro in the sci-fi epic Stardust, as well as Interview directed by Steve Buscemi.

Miller is rumoured to appear in the film version of writer Michael Chabon's novel, The Mysteries of Pittsburgh, also starring and Peter Sarsgaard. The project is slated for a 2007 release.

Miller has lent her support to design limited edition T-shirts or vests for the 'Little Tee Campaign' for Breast Cancer Care which donates money for breast cancer research. She has also agreed to design a range of jeans for Pepe.

Miller's relationship with Jude Law has frequently featured in the entertainment press. On Christmas Day of 2004, they became engaged. However, on July 18, 2005, Law issued a public apology to her for having an affair with Daisy Wright, the nanny of his children, by his former wife. Ironically, in October the media reported that she'd been conducting a simultaneous affair with actor Daniel Craig, one of Law's friends, who had appeared with Miller in Layer Cake two years previously. Despite attempts to salvage their relationship, the couple parted in time for Miller to celebrate her single status at the UK premiere of Casanova in February 2006. The latest reports from May 29, 2006 state that Miller and Law are "working things out" with their relationship.

She is frequently noted for her fashion sense and often ranks highly in "best dressed" lists; often second only to supermodel Kate Moss. She is particularly credited with popularising "boho-chic", a "look" which took off after her appearance at the Glastonbury festival in 2004. This attribution is a little controversial as many feel Kate Moss is the true originator of this look. However, it was probably the readiness with which women of differing ages could identify with Miller and her style that made it seem ubiquitous during 2004-5. Young "identikits" were often referred to as "Sienna Millers" or "Siennas".

She is also friends with the fashion designer Matthew Williamson, who has referred to her as his 'muse'.