Thirlwell was educated at the independent Haberdashers' Aske's Boys' School, Elstree. He read English at New College, Oxford, where he got the top first. He was a Prize Fellow of All Souls College, Oxford between 2000 and 2007, and worked as assistant editor at the literary magazine Areté. He now lives in London. In 2011 he was the S Fischer Guest Professor of Comparative Literature at the Freie Universität Berlin. In 2015 he was announced as an Honorary Fellow of the Metaphysical Club at the Domus Academy in Milan.

Thirlwell is the author of three novels, Politics (2003),The Escape (2009) described by Milan Kundera as "a novel where the humour is melancholic, the melancholy mischievous, and the talent startling" and Lurid & Cute (2015).

He is also the author of a project on the novel and translation, which includes a book first published in 2007, which was chosen as a book of the year by Tom Stoppard in The Guardian and A. S. Byatt in the Times Literary Supplement; and, as guest editor, an anthology of multiple translations for McSweeney's Quarterly.

An experimental book with unfolding pages called Kapow!, designed by Studio Frith, was published by Visual Editions in 2012. It was nominated for the Design Museum's 2013 Designs of the Year awards  and has been included in the permanent collection of the Art Institute of Chicago.

His writing is published in the New York Times, Le Monde, and La Repubblica, as well as the New York Review of Books, The New Republic, and The Believer. He has written columns for The Guardian and Esquire.

• Politics (2003)
• Miss Herbert (US: The Delighted States) (2007)
• The Escape (2009)
• Kapow! (2012)
• Lurid & Cute (2015)

• 2003: Granta "Best of Young British Novelists"
• 2003: Betty Trask Award, winner, "Politics"
• 2005: Lire "50 écrivains pour demain"
• 2008: Somerset Maugham Award, winner, "Miss Herbert"
• 2009: Encore Award, shortlist, "The Escape"
• 2013: Granta "Best of Young British Novelists"
• 2015: E.M. Forster Award, winner