Butterworth was born in London, England, and attended Verulam Comprehensive School, St Albans and St John's College, Cambridge. His brother Steve is a producer and brothers Tom and John-Henry are also writers.
A major influence on Butterworth's work is 2005 Nobel Literature Laureate Harold Pinter: "I know and admire Harold Pinter enormously. He has a ginormous influence on me. Conversations with him have inspired my work."
Butterworth has had major success with his play Mojo (which premiered at the Royal Court Theatre in 1995). It won the Laurence Olivier, an Evening Standard and the George Devine awards. Butterworth wrote and directed the film adaptation of Mojo, released in 1997. This featured Harold Pinter. He directed and co-wrote with his brother Tom the film Birthday Girl (2001), which was produced by his brother Steve and starred Nicole Kidman.
Butterworth also achieved positive reviews with his plays The Night Heron (which premiered at the Royal Court in 2002) and The Winterling (also at the Royal Court in 2006).
In May 2007 Butterworth received the E. M. Forster Award from the American Academy of Arts and Letters.
His play Parlour Song opened to "rave reviews" at the Atlantic Theatre Company, in New York City in March 2008.
Butterworth's fourth play for the Royal Court premiered in July 2009 to outstandingly positive reviews—the comedy Jerusalem, described as a "contemporary vision of life in [England's] green and pleasant land". Jerusalem was the second important Butterworth production in London in 2009. The production starred Mark Rylance as Johnny Byron, and featured Mackenzie Crook as Ginger in a supporting role and was a sell-out. It won the Critics' Circle Theatre Awards for 2009 and the production, with the same cast, transferred to the Apollo Theatre on Shaftesbury Avenue in January 2010. In late 2009, the play was named at number two in the Times Top Twenty Plays of the Decade.
The Almeida Theatre presented the European première of Parlour Song in March 2009.