Helen Edmundson's first play, Flying, was presented at the National Theatre Studio in 1990. In 1992, she adapted Tolstoy's Anna Karenina for Shared Experience, for whom she also adapted The Mill on the Floss in 1994. Both won awards – the TMA and the Time Out Awards respectively – and both productions were twice revived and extensively toured.

Shared Experience also staged her original adaptation of War and Peace at the National Theatre in 1996, and toured her adaptations of Mary Webb's Gone to Earth in 2004, Euripides' Orestes in 2006, the new two-part version of War and Peace in 2008, and the original play Mary Shelley in 2012.

Her original play The Clearing was first staged at the Bush Theatre in 1993, winning the John Whiting and Time Out Awards, Mother Teresa is Dead was premiered at the Royal Court Theatre in 2002 and The Heresy of Love was premiered by the Royal Shakespeare Company in the Swan Theatre in 2012.

Her adaptation of Jamila Gavin's Coram Boy premiered at the National Theatre to critical acclaim in 2005, receiving a Time Out Award. It was subsequently revived in 2006, and produced on Broadway in 2007. She adapted Calderón’s Life is a Dream for the Donmar Warehouse in 2009, and Arthur Ransome's Swallows and Amazons for the Bristol Old Vic in 2010, which subsequently transferred to the West End before embarking on a national tour in 2012.

Her adaptation of Émile Zola's Thérèse Raquin was premiered by the Theatre Royal, Bath, in 2014, and was subsequently produced on Broadway by Roundabout Theatre Company in 2015.

Her original play, Queen Anne, was commissioned and premiered by the Royal Shakespeare Company in 2015, and her adaptation of Andrea Levy's Small Island was staged by the National Theatre in 2019, revived in 2022.

She was awarded the 2015 Windham Campbell Prize for Drama.