Skrein made his acting debut in Plan B's short film Michelle. Skrein got his first lead role in Plan B's Ill Manors. Skrein portrayed Daario Naharis in the third season of the television series Game of Thrones. However, in the fourth season of the series, he had been replaced by Dutch actor Michiel Huisman. Skrein states that "behind the scenes politics" had forced him to leave the show. In 2014, Skrein was cast in The Transporter: Refueled, replacing Jason Statham as the lead. Though the film was critically panned, his performance was praised. In 2016, Skrein played the lead villain, Ajax, in the blockbuster action film Deadpool.
On 23 October 2015 Skrein was cast in sci-fi thriller, Gateway 6, alongside Rhys Ifans, with Tanel Toom making his directorial debut. Filming will commence in Estonia in the spring of 2016. On 29 October 2015 Skrein was cast in psychological revenge thriller, In Darkness, alongside Natalie Dormer and Stacy Martin; principal photography will begin early 2016.
The fast-paced action movie is again set in the criminal underworld in France, where Frank Martin is known as The Transporter, because he is the best driver and mercenary money can buy. In this installment, he meets Anna and they attempt to take down a group of ruthless Russian human traffickers who also have kidnapped Frank’s father.
When a successful New York public defender loses his first case, he is pulled into a drug heist by a former client in an effort to beat the broken system at its own game.
Jack Regan, a hardened cop who doesn’t play by the rules, is confronted with a criminal from his past. With sidekick George Carter they are put on the case of a jewellery store heist that ends in a killing. But is that killing really an execution in disguise? With pressure from his boss and the fact that Regan is having an affair with that boss’s wife, it’s not going to be easy for him to stay out of trouble.
Ensemble film revolving around characters living in Forest Gate, London. Over the course of a few days, six inter-linking stories explore issues of drug use, prostitution and urban poverty.