Nnaji was born in Mbaise, Imo State, Nigeria but grew up in Lagos, the fourth of eight children and was brought up in a middle class environment. Her father worked as an engineer and her mother as a nursery teacher. She attended Methodist Girls College (Yaba, Lagos), before transferring into the University of Lagos where she graduated with bachelor degree in creative arts. While at the university, she began auditioning for acting jobs in Nollywood.
Nnaji started her acting career as a child actress in the then popular television soap opera Ripples at the age of 8. In 1998 at the age of 19 she was introduced into the growing Nigerian film industry with the movie "Most Wanted".Her subsequent movies include Last Party, Mark of the Beast and Ijele. In 2010 she starred in the award winning film Ijé: The Journey. Nnaji has starred in over 80 Nollywood movies. Genevieve Nnaji is considered to be one of the best paid actresses in Nollywood. In 2009, she was referred to as the Julia Roberts of Africa by Oprah Winfrey.

In 2004 she signed a recording contract with EKB Records, a Ghanaian record label, and released her debut album One Logologo Line, a mix of R&B, Hip-Hop and Urban music.