Nathalie Kelley was born in Lima, Peru, to a Peruvian mother and an Argentine father. She moved to Sydney when she was 2 years old. From a young age, she dreamed about being an actress. She attended North Sydney Girls High School on Sydney's North Shore. When she was 16 she became a salsa dancer, which helped her get the money to finish her education. The "Miss Latin America competition" also earned her a much-needed $1,000, before she took a year off and went to Brazil. The things Kelley saw there prompted her to shun show business and come home to launch herself into a social science degree at the University of New South Wales. She volunteered with Indigenous Australian youth in the inner-city suburb of Redfern before moving to Los Angeles and eventually becoming a film actress.
In 2005, Charmed executive producers Brad Kern, Aaron Spelling and E. Duke Vincent developed a one-hour pilot for The WB titled Mermaid. Kelley was cast as the series protagonist Nikki, a mermaid who is rescued by a young man when she washes ashore in Miami. The pilot was not picked up as a result of The WB and UPN merging into The CW; the resulting network passed on the show. Kelley has since appeared on both Lone Star and CSI: Crime Scene Investigation.
In June 2006, Kelley received her breakout role in the film The Fast and the Furious: Tokyo Drift, the third installment of the Fast and the Furious movie series. Kelley played the role of an Australian schoolgirl attending a Japanese high school (a role she would later reprise nine years later in Furious 7 through the use of archival footage). The film made over $158 million worldwide. In March 2008, Kelley appeared in the low-budget drama crime film Loaded alongside Jesse Metcalfe. In March 2011, Kelley had a small role in the retro comedy film Take Me Home Tonight, which starred Topher Grace, Anna Faris and fellow Australian Teresa Palmer. The film was shot in Los Angeles in 2007 but its release was delayed by Universal Pictures for unknown reasons. The following month, Kelley appeared as the protagonist in the low-budget horror film Urban Explorer, which follows a group of four urban explorers who explore an underground world beneath metropolitan Berlin.
In 2010, Kelley played the love interest in the music video for the Bruno Mars song "Just the Way You Are".
In August 2011, Kelley signed on in a major recurring role in the second season of the ABC crime drama television series Body of Proof. Kelley appeared as Dani Alvarez in ten episodes and made her final appearance in the episode "Going Viral Part One".
In 2012, Kelley played a vampire princess in the video clip "Luna Llena" from Puerto Rican reggaeton duo Baby Rasta & Gringo. In 2014, she won a regular role in the Lifetime series UnREAL.
In fall of 2016, Kelley appeared in the eighth and final season of The Vampire Diaries as Sybil.