At university, Whittle began modelling, becoming the face of a Reebok campaign in 2000. This brought him to the attention of casting agents for Sky One's Dream Team, who cast him as Ryan Naysmith.
In August 2009, Whittle was announced as a contestant on the BBC One reality series Strictly Come Dancing, paired with Australian professional Dancer Natalie Lowe. A fellow contestant on the programme, Ali Bastian, also starred with him in Hollyoaks. Whittle made it through to the final of the competition (beating Rav Wilding, to whom he had lost The Weakest Link in 2008), and competed against television presenter Chris Hollins and his dance partner Ola Jordan for the Strictly Come Dancing glitterball trophy. However, Whittle lost the battle and ended up taking second place, despite winning the judges' scores 190–186.
After playing his first gay character on BBC One's Holby City, Whittle played Calvin Valentine in the Channel 4 soap opera Hollyoaks until May 2010, when his character was killed off after Whittle decided to depart. In January 2008, Whittle appeared on a Celebrity edition of The Weakest Link, reaching the final, but losing out to Crimewatch UK star, Rav Wilding.
In July 2012, Whittle appeared as Charles on season 2 of Single Ladies. He also appeared as Captain George East in Stephenie Meyer and Jerusha Hess's romantic comedy Austenland, which was completed in 2012. In March 2013, Whittle appeared in the American drama series NCIS, guest-starring in the Season 10 episode, "Detour". In 2014, he began a recurring role in The 100 as a Grounder named Lincoln, and was upgraded to regular status for season 2. He left the show, claiming that showrunner Jason Rothenberg "bullied" him off the show. He also played the role of Daniel in season 2 the Mistresses.
In 2014, Whittle became known to American audiences after appearing as Daniel Zamora in the ABC television series Mistresses. The same year, he also began starring in The CW's post-apocalyptic drama The 100, playing the role of Lincoln, a "Grounder". Whittle also had a recurring role on VH-1's Single Ladies in 2012.
On 28 January 2016, Whittle was announced as the lead character, Shadow Moon, in the Starz television series American Gods.
