Bremner caught the eye of the film world with his appearance against David Thewlis in Mike Leigh’s Naked (1993). He went on to portray Spud in Danny Boyle’s film adaptation of Irvine Welsh’s 1993 novel Trainspotting, and later Mullet, a street thug in Guy Ritchie’s Snatch. In the 1994 stage version of Trainspotting, Bremner played the lead role of Mark Renton, the role played by Ewan McGregor in the 1996 film. He has played supporting roles in blockbusters such as Pearl Harbor and Black Hawk Down, in which he appeared alongside Trainspotting co-star Ewan McGregor (which he has again since, in Perfect Sense and Jack the Giant Slayer). In 2005, he had a small role in the mini-series Elizabeth I as James VI, King of Scots. In December 2006, he played Harold Stritzke in the Sci Fi Channel miniseries The Lost Room. In 2007, he played Robert Louis Stevenson in the BBC Four documentary Ian Rankin Investigates Dr. Jekyll and Mr. Hyde, as well as Justin in Death at a Funeral.

In 2017, Bremner reprised his role as Spud in T2 Trainspotting, the sequel to Trainspotting, for which he was awarded the BAFTA Scotland Award for Best Actor.

In 2017 he produced the short film No Song to Sing.