In film, she has starred in the action thriller Ronin (1998), the psychological comedy-drama The Truman Show (1998) and the science fiction drama Solaris (2002).

[5] She appeared the following year, again credited as "Natascha Taylor," in the series Bergerac as Louise Calder, a rebellious daughter of very wealthy parents.

[7] She had leading roles opposite Brad Pitt in The Devil's Own (1997), Robert De Niro in Ronin (1998)[8] and George Clooney in Solaris (2002).

McElhone starred in a 2006 West End production of Honour at the Wyndham's Theatre alongside Diana Rigg and Martin Jarvis.

She accepted the role as Karen in the Showtime cable television series Californication, alongside David Duchovny.

[15] In February 2016, McElhone was cast alongside Kiefer Sutherland in ABC's political drama series Designated Survivor, which premiered in September 2016.

[21] On 20 May 2008, 43-year-old Kelly was found slumped in the doorway of his family's home by a fellow doctor, who had him rushed to Chelsea and Westminster Hospital (where he worked).

[22][23] After her husband's death, McElhone continued to write letters to him, sometimes documenting the daily trivia of life but also dealing with how she and their young children were coping with their loss.