Mitra was born in Paddington, London, England, to Nora Downey and Anthony Mitra, a cosmetic surgeon of Bengali Indian and English descent, and her mother is Irish. When Mitra was eight years old, her parents divorced, and she was sent to boarding school. She spent several years at two different schools, including Roedean, but Mitra claims she was eventually expelled from both of them.
Mitra's first major role came as Scott Wolf's illicit love interest on the television series Party of Five in 1994. In 2000, she had a small but key role in the film Hollow Man, playing the rape victim of Kevin Bacon, an incident that drives his character insane. She then had a main role in the medical drama Gideon's Crossing, playing the character Dr. Alejandra Ollie Klein.
Mitra's subsequent roles include Ali G Indahouse, Sweet Home Alabama, Stuck on You, and leading roles in Highwaymen and Spartacus. She also appeared in the final season of The Practice, playing the character Tara Wilson, and continued that role into its spin-off Boston Legal, but left not long into the second season. In 2005, Mitra played the role of Kit McGraw during Season 3 of Nip/Tuck.
Mitra's other notable roles include Skinwalkers, The Number 23, and Shooter. In 2008, she starred in the lead role of the science fiction/action film Doomsday, playing the character Major Eden Sinclair, and in 2009, she starred in Underworld: Rise of the Lycans, playing the character Sonja, the daughter of the powerful vampire elder Viktor.
Mitra has also been recognized for her work as the live-action model for Lara Croft, the lead character in Eidos Interactive's Tomb Raider video game series. She was ranked #46 on the Maxim Hot 100 Women of 2001.
