[4] She played feminist lecturer Dr Robyn Penrose in the BBC television mini-series dramatisation of David Lodge's Nice Work in 1989.

The character of Dr Graham was written out of the show at the end of series 9 (episode 13) when she was fatally shot whilst intervening in a conflict between a man and his daughter.

[7] Her theatre work included regional and London-based appearances, from the Octagon, Bolton, in Hedda Gabler, to Richard Cheshire's Way of the World appearing in West End productions of Ziegfeld as Billie Burke (1988),[8] City of Angels and Billy Elliot the Musical at the Victoria Palace Theatre, for which she was nominated for an Olivier Award.

[13][14] She guest starred in the BBC TV series Sherlock in the episode "The Great Game" (2010), as a museum curator, Miss Wenceslas.

[17][18] She starred in Shakespeare's play Richard III alongside Kevin Spacey at The Old Vic in London during summer 2011 as part of the Bridge Project.

[22] In 2015 she starred alongside Tamsin Greig in the new musical Women on the Verge of a Nervous Breakdown, based on the Pedro Almodóvar film, at The Playhouse in London.

[citation needed] In the same year, she played Camilla, Duchess of Cornwall, in the Channel Four sitcom The Windsors, which presents a parodic version of the British royal family.

[29] In 2023, Gwynne starred as Pam Lee, a version of the real-life judge Prue Leith, in The Great British Bake Off Musical,[30] and as Stanley Baldwin in Jack Thorne's play When Winston Went to War With the Wireless at the Donmar Warehouse.

[33] In 2024, Gwynne posthumously won the Laurence Olivier Award for Best Actress in a Supporting Role at that year's ceremony, for her performance in When Winston Went to War With the Wireless.

In August 2014, she was one of 200 public figures who were signatories to a letter to The Guardian opposing Scottish independence in the run-up to September's referendum on that issue.