Madekwe was born in East London, England to a Nigerian-Swiss father and an English mother. She attended the Royal Academy of Dramatic Art in London where she gained a BA in acting. While attending the school, she appeared in numerous stage productions including King Henry V as Princess Katherine and Wuthering Heights as Catherine Earnshaw.
Madekwe started her acting career with a film titled Storm Damage. Since then, she has made guest appearances on Teachers, Doctors, Casualty, and Drop Dead Gorgeous. Madekwe landed her first motion picture in the 2007 Woody Allen film Cassandra's Dream, opposite Colin Farrell and Ewan McGregor.
Following that success, she played Elisha in the one-off BBC Three drama pilot West 10 LDN, and appeared in six episodes of Trexx and Flipside as Ollie. In 2008, she landed the role of Bambi on the ITV2 drama series Secret Diary of a Call Girl which eventually was picked up by Showtime in the United States, appearing in series two and three. Madekwe starred in the 2008 comedy film How to Lose Friends & Alienate People. Her theatre credits include Little Sweet Thing by Roy Williams and Flight Path by David Watson.
Madekwe made her official US debut in the 2009 drama series The Beautiful Life which aired on The CW. In February 2011, she was cast as Ashley Davenport in the ABC drama series Revenge. After being a regular for the first two seasons, it was reported in late May 2013 that Madekwe would depart the series following a guest appearance in the first episode of the third season.
She is currently starring in the television series Salem.
In addition to her acting career Madekwe runs a successful fashion blog called Ring My Bell