He was born in 1985 in the United Kingdom, the son of Lucy Appleby and Timothy Lloyd-Hughes, a long-time senior executive with Deutsche Bank. He has a younger brother, actor Ben Lloyd-Hughes. They both acted in Miliband of Brothers. Fred Macpherson, lead singer of the band Spector, and formerly of Les Incompétents and Ox.Eagle.Lion.Man, is his cousin.
Lloyd-Hughes first appeared in the TV series Murphy's Law in 2004 before playing Roger Davies in the 2005 film Harry Potter and the Goblet of Fire. He then appeared in Joanna Hogg's film Unrelated in 2007 alongside Tom Hiddleston.
From 2008–2010 he played school bully Mark Donovan in the British sitcom The Inbetweeners. He reprised the role in the film The Inbetweeners Movie in 2011. In 2010, he portrayed former British Labour Party Politician David Miliband in the TV film documentary Miliband of Brothers.
In 2011, he starred in the film Dimensions as Stephen, a brilliant young scientist who lives in England in the 1920s. The same year, he appeared in the film Weekender about the 1990 Manchester rave scene.
In 2012, he starred as Dimitri Mitropoulos in the play Posh, which played at the Duke of York’s Theatre. Michael Billington of The Guardian said of Lloyd-Hughes's performance that he "impresses as a wealthy Greek who aims to be more English than the English".
Lloyd-Hughes played Charles Bovary in the drama film Madame Bovary with Mia Wasikowska in the title role and which was released in 2014.
