He appeared in films such as Black Beauty (1994), Restoration (1995), James and the Giant Peach (1996), Dragonheart (1996), Seven Years in Tibet (1997), Gangster No.

Other film roles include Kingdom of Heaven (2005), The Boy in the Striped Pyjamas (2008), War Horse (2011), The Theory of Everything (2014), Anomalisa (2015), Wonder Woman (2017), I'm Thinking of Ending Things (2020), and Enola Holmes 2 (2022).

Thewlis's most notable television roles include V. M. Varga in the third season of FX's Fargo (2017), the voice of the Shame Wizard in the Netflix animated sitcoms Big Mouth (2017–present) and Human Resources (2022–2023), Christopher Edwards in the HBO miniseries Landscapers (2021), John Dee in the Netflix drama series The Sandman (2022), and Fagin in the Disney+ TV series The Artful Dodger (2023).

[7] He went on to play small roles in high-profile series such as BBC's Only Fools and Horses in 1985 and The Singing Detective in 1986, before being offered a more significant part in Alan Clarke's Road and in the ITV sitcom Valentine Park in 1987.

[8] His first big-screen leading role was opposite Clive Owen in Vroom, directed by Beeban Kidron in 1988, and he starred in Paul Greengrass's anti-Falkland War drama Resurrected in 1989, playing a presumed-dead soldier who returns to Britain.

That same year, he appeared on television as a sexual predator named James Jackson in Prime Suspect 3, opposite Helen Mirren and Ciarán Hinds.

[citation needed] During the 1990s, Thewlis appeared in a variety of films, mostly fantasy and period, including Restoration (1995), Black Beauty (1994), Total Eclipse (1995) with Leonardo DiCaprio, The Island of Dr. Moreau (1996), Dragonheart (1996), and Seven Years in Tibet (1997), opposite Brad Pitt.

Notable appearances include Bernardo Bertolucci's Besieged (1998), the Coen brothers' The Big Lebowski (1998), and Paul McGuigan's Gangster No.

[citation needed] He auditioned for the role of Quirinus Quirrell in the Chris Columbus directed film Harry Potter and the Philosopher's Stone, but the part went to Ian Hart.

[citation needed] He appeared as an SS Commandant of a Nazi death camp and father of the main character in The Boy in the Striped Pyjamas, which was well received.

[citation needed] He has voiced the Shame Wizard in the Netflix animated sitcom Big Mouth (2017–present) and its spin-off Human Resources (2022–2023).

[16] Thewlis's black comedy novel set in the art world, The Late Hector Kipling, was published by Simon & Schuster in 2007.