Clarke was born in London, England and grew up in Berkshire. Clarke's father is a theatre sound engineer,her mother is a business woman, and her brother is studying politics. Clarke's interest in acting began at the age of three after seeing the musical Show Boat which her father was working on at the time.She was educated at Oxford's St Edward's (2000–2005)and Rye St Antony (2005–2007) before studying at Drama Centre London where she graduated in 2009.
Clarke's early work includes two plays at St. Edwards, ten plays at Drama Centre London, the 2009 Company of Angels production of Sense, and a 2009 commercial for Samaritans.Her first television roles were Saskia Mayer in a 2009 episode of Doctors and Savannah in SyFy's 2010 movie Triassic Attack.
The actress's big break came when she was cast as Daenerys Targaryen in the HBO medieval fantasy series Game of Thrones which is based on the book series A Song of Ice and Fire by George R. R. Martin. She was cast as a replacement to fellow British actress Tamzin Merchant who dropped out of the pilot for undisclosed reasons. The show debuted in April 2011 to positive reviews and was quickly picked up by the network for a second season.Clarke won the 2011 EWwy Award for Best Supporting Actress in a Drama for her role as Daenerys.
Clarke will appear in the film Overdrive in 2012.