Harry Potter films: 1-7 - Ripper Street

Lewis has been acting since he was five years old. He started off with minor roles in television programmes, debuting in Some Kind of Life.

He then went on to play Neville Longbottom in the eight Harry Potter films.

During the filming of Harry Potter and the Order of the Phoenix, Helena Bonham Carter, who portrays the character Bellatrix Lestrange, accidentally ruptured Lewis's eardrum when she stuck her wand in his ear.

The author of the Harry Potter series, J. K. Rowling, gave a speech during the final world premiere of Harry Potter and the Deathly Hallows Part 2 on 7 July 2011 in London, England. She stated that there were seven major cast members in the series, whom she referred to as The Big Seven, and she named Lewis as one of the seven members, along with Daniel Radcliffe, Rupert Grint, Emma Watson, Tom Felton, Evanna Lynch, and Bonnie Wright.

Shot prior to the release of Deathly Hallows, Lewis played the reporter in the independent film The Sweet Shop. Lewis played the character Jamie Bradley in a five-part TV series called The Syndicate written by Kay Mellor, which was broadcast on BBC One in spring of 2012.

In July 2012, Lewis appeared in a music video called Filth by A Band of Buriers; Matthew co-starred with actress Lily Loveless, who together, portrayed boyfriend and girlfriend in the video.  Lewis played the role of Dodd in the 2012 film Wasteland (known in the UK as The Rise), written and directed by Rowan Athale.^[13] The film was screened at the Newport Beach Film Festival on Sunday, 28 April 2013 and Monday, 29 April 2013.^[14] Lewis also stars as Patrick in Me Before You which was released in theaters in June 2016.

In 2011, Lewis played Lester Cole in his stage debut in Agatha Christie's Verdict touring stage production.

In June 2012, Lewis was confirmed to play the character Mick in the West End stage new production of Our Boys by Jonathan Lewis. The role marked Lewis's West End debut. He starred in the play alongside Cian Barry, Arthur Darvill, and Laurence Fox. The play started its previews on 26 September 2012 and played regularly from 3 October 2012 until 15 December 2012 at the Duchess Theatre, London.

In July 2016, it was announced that Lewis is the star in a stage production called ‘‘Unfaithful’’ playing the character called ‘‘Peter‘‘. The play was directed by Adam Penford, with playwright by Owen McCafferty. The play performance started on the 25 August 2016 and ended 8 October 2016. In the play, Lewis was co-starring alongside Sean Campion, Niamh Cusack, and Ruta Gedmintas

In 2017, Lewis, a personal friend of American comedian Sal Vulcano, made an appearance on Impractical Jokers as himself, where he filled in for Vulcano, in one of the challenges in the IJ episode, "Universal Appeal", which was shot at Universal Orlando.