Gwilym Lee began his career while he was still a teenager and starred in the television adaptation of the ‘Animal Ark’ children’s book series. The series, wherein he played the role of James Hunter, ran for two seasons from 1997 to 1998 (13 episodes). Following this he played the role of Edward, Prince of Wales in the Royal Shakespeare Company's production of ‘Richard III’. Thereafter, he took a break from acting to complete his education. He returned to acting in the year 2008 and worked in a short film ‘The Escort’, an episode of TV series ‘Mutual Friends’ and National Theatre's production of ‘Oedipus’. His work in ‘Oedipus’ won him commendation at the ‘Ian Charleson Awards’. He continued to work in theatre and the next two years saw him in more theatre productions. These include ‘About Tommy’ (2009), ‘Hamlet’ (2009), ‘The Fairy-Queen’ (2010), ‘Danton's Death’ (2010) and 'King Lear' (2010–2011). His portrayal of Edgar in 'King Lear' won him the First Prize at the ‘Ian Charleson Awards’. In 2010, he was also seen in the role of a Senior Technician Mountain in the romantic thriller film 'The Tourist' and D.C. Block in the action crime thriller movie ‘Isle of Dogs’. On television, he acted in an episode each of TV series ‘Inspector Lewis’ (2009), ‘Waterloo Road’ (2009), ‘Ashes to Ashes’ (2009) and ‘Doctors’ (2010).
Gwilym Lee then played the leading role of Reverend Henry Jameson in the final series of BBC One period drama series ‘Land Girls’ (2011). Earlier, the role was played by Liam Garrigan in the second season of the series. In 2011, he narrated the TV Movie documentary ‘Children of 9/11’ and in 2013, once again, turned narrator for another TV movie documentary ‘Catching a Killer: Crocodile Tears’. In 2012, he played the role of Sean Gilmartin in the TV movie ‘Restless’ and acted in an episode each of the TV series ‘The Hollow Crown’, ‘Fresh Meat’ and ‘Monroe’. In 2013, he joined the cast of the 16th season of the popular crime drama television series ‘Midsomer Murders’ and played the role of DS Charlie Nelson in it till 2016 (15 episodes). In 2015, he was seen in the role of James in BBC One’s TV movie ‘A Song for Jenny’.
In 2017, Gwilym Lee played the role of Alistair in the short film ‘The Agency’ and turned narrator for the documentary series ‘The Royal House of Windsor’. The same year, he portrayed the character of Samuel Castell in the first season of Sky One's television drama series ‘Jamestown’. This was followed by a couple of film releases in 2018 – the British-Polish thriller film 'The Last Witness' and the biographical musical drama film 'Bohemian Rhapsody'. In the former, he played the role of John Underwood while in the latter, he was seen in the role of the rock band Queen's guitarist Brian May. The film won him, along with other cast members, a nomination at the ‘Screen Actors Guild Awards’ (Outstanding Performance by a Cast in a Motion Picture). In 2019, he had yet another film release – the Australian romantic comedy ‘Top End Wedding’ in which he played the role of Ned. It received critical acclaim. The same year, he was seen in an episode of TV series ‘The Man’.
In 2020, Gwilym Lee became a part of Hulu's historical and satirical black comedy-drama series 'The Great' and played the main role of Grigor Dymov in its first two series till 2021. The drama series earned critical acclaim and once again won nomination at the ‘Screen Actors Guild Awards’ in the category of Outstanding Performance by an Ensemble in a Comedy Series. His theatre credits of the decade include ‘Othello’ (2011), ‘The Promise’ (2012), ‘Versailles’ (2014) and ‘Diminished’ (2017).
In his career, Gwilym Lee has also lent his voice in various video games. These include ‘Cloud Chamber’ (2013, role: Tom), 'Dragon Quest Heroes: The World Tree's Woe and the Blight Below' (2015, role: Psaro the Manslayer), 'Final Fantasy XIV: Heavensward' (2015, role: Cid), 'Final Fantasy XIV: Shadowbringers' (2019, role: Cid), 'South of the Circle' (2020, role: Peter Hamilton) and ‘Final Fantasy XIV: Endwalker’ (2021, role: Cid).
When Frank Tupelo meets a beautiful woman, Elise, on board a train to Venice, he takes it as a chance encounter. However, soon he finds himself being chased by Inspector John Acheson as well as a mobster, Reginald Shaw, both of who believe that he is the wanted Alexander Pearce who has undergone a surgery to change his face.