Duncan was born in 1988 in Croydon, London, England. Her mother is Jamaican and her father half English, half Greek. She moved to Nottingham in 1991, where she grew up. She displayed a keen interest in music as a child and at age 3 composed her first original tune on a tiny toy keyboard. She commenced piano lessons at age 5 and, preferring to learn by ear rather than by conventional sight reading, she pursued the ABRSM Jazz Piano syllabus, obtaining her grade 5 qualification when she was 14. Her musical influences were quite eclectic – her father had an extensive record collection with a large black music content, as a young child she listened to classical music on The Magical Music Box, and she was taken to see Jools Holland and his Big Band on her 11th birthday, whilst all the time listening to a wide array of music of her choice. Duncan first sang in public at age 10 in Junior school, and at age 15 she won the year 11 music competition at her Secondary school, singing and playing an Alicia Keys cover. She had also been writing her own songs from quite an early age. She left school to attend New College Nottingham where she obtained a BTECHNC in music in 2007.
Duncan started off playing solo gigs at open mic venues around Nottingham, and singing with local bands, before signing to local record label Farmyard Records, for whom she recorded the EP Natalie Alexis Duncan, (no longer available) in 2009. Her break came in 2010 when she featured in a programme the BBC were making about 12 young musicians from around the UK, who had used music as a means to overcome various difficulties they had all experienced. The programme was the brainchild of drum and bass pioneer Goldie; a three part series, Goldie's Band By Royal Appointment told each young musician's story, then set them all the task of writing 12 songs to be performed at a live concert in Buckingham Palace in front of special guest Prince Harry. Following this she was signed by Verve Records, and recorded her debut album Devil in Me at Peter Gabriel's Real World Studios. Produced by Joe Henry it was recorded "live" in just two weeks with renowned session musicians Greg Cohen, Earl Harvin, John Smith and Patrick Warren. The album was released in 2012 to critical acclaim. In September of that year she appeared on the BBC programme Later... with Jools Holland, the same episode also featured the British rock band Muse, who she went on to support at the commencement of their European tour. She also provided vocals for the Disclosure track "Apollo", from Settle: The Remixes. She included a cover of the Etta James hit "At Last" on her "Find Me A Home" EP. The song was featured in an advert for Auto Trader in the UK.