He has appeared in Guy Ritchie's Lock, Stock and Two Smoking Barrels, as well as in television shows such as the comedy drama Hotel Babylon and the HBO series Band of Brothers and, earlier in his career, starred as Spike Thomson in the comedy drama Press Gang.

He replaced Bryan Singer as director of Bohemian Rhapsody, a biopic about the band Queen, released in October 2018; due to DGA rules, he received executive producer credit.

As a youth actor he was regularly featured in British productions in the early 1980s, including The Long Good Friday, The Elephant Man and The Bounty.

As an adult he appeared on television as the rebellious teenager Spike Thomson in Press Gang and in Murder Most Horrid (1991) with Dawn French.

He has also starred in the films Caravaggio (1986), The Rachel Papers (1989), Lock, Stock and Two Smoking Barrels (1998), Layer Cake (2004), AffirmFilm's Solomon as Rehoboam and Universal's Doom.

He played a brief role in the BBC series New Tricks, in the episode "Final Curtain", as an actor named Tommy Jackson.

Fletcher has been the voice for McDonald's television adverts and (feigning a US accent) is the narrator of The Game audio book written by Neil Strauss.

In December 2017, Fletcher was announced as Bryan Singer's replacement director on the Queen biopic Bohemian Rhapsody.