Sykes was born on 18 April 1993 to Harry and Karen Sykes. He has a younger sister, Jessica Sykes, who is also a singer. Sykes attended Sylvia Young Theatre School and Ribston Hall High School sixth form.

Sykes started singing when he was six years old. In 2003, he won various competitions, including Britney Spears’ Karaoke Kriminals and Cheltenham Competitive Festival of Dramatic Art. In 2004, he appeared on ITV’s Ministry of Mayhem, and won the Door Youth Project’s “Undiscovered Youth Talent Contest” where he performed “Mack the Knife” in Derker, and he attempted to represent United Kingdom in the Junior Eurovision Song Contest 2004 that was held in Lillehammer. In the finals, he finished in third place with the song, “Born to Dance”, behind Cory Spedding and runner-up Andrew Merry. In 2008, he performed for the music competition “Live and Unsigned”.

In 2009, at the age of 16, Sykes auditioned for the boy band The Wanted. The auditions were held by Jayne Collins. Sykes was chosen to be one of those five members for a group. He joined bandmates Max George, Siva Kaneswaran, Tom Parker and Jay McGuiness. The band achieved 10 UK top 10 singles as well as 3 UK top 10 albums. Sykes as a member of the group has sold more than 10 million records. After enjoying much mainstream international success, in 2014, the band decided to take a break and pursue their personal endeavours after a tour of the United Kingdom and the United States.

In the summer of 2012 he dated Dionne Bromfield He then dated Ariana Grande from August to December 2013. On Nathan’s birthday, April 18, 2013, Nathan went in for surgery to remove a nodule in his throat. During episodes of The Wanted life, he was talking about his throat hurting and burning. The day manager, Nano, had him see a specialist, who concluded he had a nodule on his throat and suggested that it be removed. When he recovered, he sang his solo in “I Found You” at the Summertime Ball in 2013, surprising the fans when he appeared.

At the same time, Sykes and American singer Ariana Grande released their collaborative single, “Almost Is Never Enough”. In 2014, Sykes signed a record deal with Global Entertainment (a part of the Global Group, along with Capital’s owner Global Radio). In June 2014, he joined singer Jessie J on stage for Capital’s Summertime Ball to perform “Calling All Hearts”.

In March 2015, Sykes debuted his first solo music video for “More Than You’ll Ever Know” on Vevo. Sykes went on his first solo tour on 8 April 2015, which included six sold-out shows in the United Kingdom. Sykes announced via the app Periscope that his debut single would be called “Kiss Me Quick”. The single was released on 5 July 2015. On 21 May 2015, Sykes released his music video for his debut single, “Kiss Me Quick” on Vevo. The song peaked at number 14 on the UK Singles Chart.

In October 2015, Sykes announced his second single, called “Over and Over Again”. The music video for the song was released in the UK on 28 October 2015. It was released worldwide on 20 November 2015. It was also announced that Sykes would support Little Mix on their The Get Weird Tour in March 2016. Sykes announced that his third single, called “Give It Up”, would be released on 13 May 2016. The music video for “Give It Up” was released on 27 April 2016, and was later banned from television after featuring numerous scenes which came across as unsuitable for most audiences.

On 11 June 2016, Sykes performed at Capital’s Summertime Ball for the seventh consecutive time (2010, 2011, 2012, 2013 with The Wanted, 2014 as Jessie J’s guest, 2015 and 2016 as a solo performer).

On 11 July 2016, Sykes announced via Twitter that he would be joining Alessia Cara on her Know-It-All headling tour in the United States. On 12 October 2016, Sykes announced via Twitter that his debut studio album, Unfinished Business would be out worldwide on 11 November 2016.