Prebble grew up in Haslemere, Surrey, and was educated at Guildford High School. While studying English at the University of Sheffield, Prebble wrote a short play called Liquid, which won the PMA Most Promising Playwright Award. She received the Distinguished Alumni Award in 2014.
2007 saw the premiere of Prebble's first television series, Secret Diary of a Call Girl, starring Billie Piper. Prebble wrote for the first two of the show's four seasons, the last of which concluded in March 2011.
Her next theatre project was ENRON, based on the financial scandal and collapse of the American energy corporation of the same name, was produced by theatre company Headlong at the Chichester Festival Theatre in 2009, under the direction of Rupert Goold. The production transferred first to the Royal Court and subsequently to the Noël Coward Theatre. The play earned Prebble an Olivier Award nomination for Best New Play. The production's Broadway transfer opened at the Broadhurst Theatre in April 2010 but failed to match the critical acclaim it received in the UK and closed the following month.
The Effect, which premiered at the National Theatre in 2012, won the 2012 Critics' Circle Award for Best Play. The Effect premiered in the US Off-Broadway at the Barrow Street Theatre on 2 March 2016, directed by David Cromer, and featuring Kati Brazda, Susannah Flood, Carter Hudson and Steve Key.
In June 2018 Prebble was elected Fellow of the Royal Society of Literature in its "40 Under 40" initiative. The same month saw the premiere of Succession, the HBO series about a global media family for which Prebble serves as both co-executive producer and writer.
In October 2018, London's Old Vic announced Prebble's A Very Expensive Poison, a stage adaptation of Luke Harding's non-fiction book of the same name. The play is about the assassination of Alexander Litvinenko by means of the invisible radioactive isotope polonium-210. 
- Liquid, 2002
- The Sugar Syndrome, Jerwood Theatre Upstairs, London, November 2003
- ENRON, Chichester Festival Theatre / Royal Court Theatre / Noel Coward Theatre, London, 2009; Broadhurst Theatre, New York City, 2010
- The Effect, National Theatre, 2012; Barrow Street Theatre, New York City, 2016
- Tim Adams (5 July 2009). "'I hate to be told somewhere is out of bounds for women.' Enter Enron". The Guardian.
- Dominic Cavendish (29 Dec 2009). "Lucy Prebble interview for Enron". The Telegraph.
- ALASTAIR GEE (17 February 2010). "Drama! Music! Financial Shenanigans!". The New York Times.
- Andy Barker (2009-07-24). "Introducing... Playwright Lucy Prebble". The Evening Standard Magazine.
- "'Enron' playwright, Lucy Prebble, receives Distinguished Alumni Award" sheffield.ac.uk, 24 July 2014
- Edwardes, Jane. "The Critics' Circle Theatre Awards 2012" criticscircle.org.uk, 16 January 2013
- Clement, Olivia. "David Cromer Sets Cast for Lucy Prebble's 'The Effect' Off-Broadway" playbill.com, 28 January 2016
- Flood, Alison (2018-06-28). "Royal Society of Literature admits 40 new fellows to address historical biases". the Guardian. Retrieved 2018-07-03.
- "Spies, assassins and strip clubs: death of Alexander Litvinenko adapted for stage".
- The Effect Archived 22 November 2012 at the Wayback Machine nationaltheatre.org.uk, accessed 29 January 2016
- Lucy Prebble at Doollee.com Playwrights Database
- "Enron: much ado about money", Prospect, Michael Coveney