Cilmi was born on 10 October 1991 in the Melbourne suburb of Dandenong. She lives with her parents Paula and Joe (whose origins are in Calabria, Italy) and her brother Joseph. She attended Sacred HeartGirls College, but now continues her education via correspondence. At an early age she developed an interest in a wide range of musical styles, including Nina Simone, Led Zeppelin, Janis Joplin, The Sweet, T.Rex and Cat Stevens. Despite her natural aptitude and vocal talent, she was told that she lacked the discipline necessary to pursue a singing career. Idolizing Janis Joplin, during this time she sang with a band performing cover songs by Led Zeppelin, Jet, Silverchair and others. Cilmi recorded original songs with writer/producers Barbara and Adrian Hannan of The SongStore.

In 2004, she captured the attention of Michael Parisi, a record company executive from Warner Music, while giving an impromptu rendition of the Rolling Stones song "Jumping Jack Flash" at the Lygon Street Festa, a community festival in Melbourne. At the age of thirteen, Cilmi travelled to the US and UK with Adrian Hannan and was offered four major US deals. She eventually signed a contract with Island Records UK.

The tracks "Don't Tell Me" and "Sorry", co-written with Barbara and Adrian Hannan, appeared on the soundtrack of 2005 Australian film Hating Alison Ashley. Cilmi made her UK TV debut on 14 December 2007 when she sang her new single "Sweet About Me" on Later with Jools Holland. In December 2007 Cilmis song "Sanctuary" featured in the film St Trinian.

In January 2008 Cilmi supported Rufus Wainwrighton his Australian tour. In February 2008 she supported the Parisian band Nouvelle Vague on their UK tour. Cilmi first album Lessons To Be Learned was written and recorded with hit production team Xenomania and was released on 31 March 2008 in the UK. She has been compared to Amy Winehouseand also Macy Gray, because of the occasional fracture in her voice.