She grew up in Notting Hill and attended Fox Primary School. At the age of 11, she moved with her family to Isleworth and attended the Green School. Following success at her A-levels, she had been planning to study philosophy at Cambridge, but chose to pursue an acting career after being spotted by Julian Fellowes in a school play.
Her maternal grandmother was Russian, and Myles refers to herself as "half-Welsh, half-Russian". Since 1996, Myles has appeared in a number of films and television productions. In 2001, she got a small role as Victoria Abberline in the thriller film From Hell.
She had a supporting role in the 2003 film Underworld and its sequel Underworld: Evolution (in a brief flashback scene).
In 2003, she starred in the thriller Out of Bounds and played Lady Penelope in Thunderbirds. In 2006, she co-starred as Isolde in the romantic drama Tristan and Isolde.
Myles appeared as Madame de Pompadour in the 2006 Doctor Who episode "The Girl in the Fireplace". She co-starred in 2006"s comedy film Art School Confidential.
Also in 2006, she appeared as Lucy Westenra in a British Broadcasting Corporation adaptation of Dracula.
In 2007, she played Freya in Outlander. Myles was cast in the Columbia Broadcasting System supernatural television drama Moonlight. In 2010, she joined Spooks, a British Broadcasting Corporation series about a counter-terrorism unit in MI5, for its ninth series, playing Beth Bailey.
She appeared in Transformers: Age of Extinction (2014).
In 2004, Myles was in a relationship with actor Charles Dance. They met while working on The Life and Adventures of Nicholas Nickleby.
From 2005 to 2007, she dated actor David Tennant, with whom she had acted in Foyle"s War and the Doctor Who episode "The Girl in the Fireplace".