2016–present: Fleabag, television, radio and theatre
In 2016, Clifford had her breakthrough screen acting role in Waller-Bridge's Fleabag, as Claire, Fleabag's uptight older sister. Waller-Bridge wrote the character of Claire with Clifford in mind, and Clifford said she fought the BBC to include her in the series, having wanted someone famous to fill the role. Fleabag returned in 2019. Clifford's performance in the show was widely praised and she was nominated for the Emmy Award for Supporting Actress in a Comedy Series and the Critics' Choice Award for Supporting Actress in a Comedy Series for her performance. In 2020, she won the BAFTA Television Award for Best Female Comedy Performance for the series. She was also nominated for the 2020 Screen Actors Guild Awards for Best Actress (which Waller-Bridge won).
In 2017, Clifford was part of the cast of the play Gloria at Hampstead Theatre, which was the play's Off West End premiere.
In 2018, Clifford had a recurring role in the ITV miniseries Vanity Fair and was in a production of Circle Mirror Transformation in Manchester.
Later in 2018, Clifford was part of the cast in the West End production of Consent at the Harold Pinter Theatre.
In 2019, Clifford had a small role in the independent dark comedy film A Serial Killer's Guide to Life. In 2020, Clifford had guest roles on the television shows Hitmen on Sky One and Liar. She starred as Diana Ingram opposite Matthew Macfadyen (who played Charles Ingram) in the April 2020 miniseries Quiz, based on the 2001Who Wants to Be A Millionaire? scandal. Clifford later co-starred in the Sky comedy series Two Weeks to Live.
In 2021, Clifford starred in the romantic comedy Good Grief, a hybrid of theatre and film produced in the context of the covid pandemic. It was written by Lorien Hayes, directed by Natalie Abrahami and featured music composed by Isobel Waller-Bridge.
In May 2021, Clifford starred as Iris in the Inside No. 9 episode "Lip Service". In July 2021, Clifford voiced GS-8 in Star Wars: The Bad Batch.
In 2022, Clifford starred in the BBC adaptation of Kate Atkinson's novel Life After Life. Clifford played Sylvia, the mother of the protagonist, Ursula Todd. She also starred in See How They Run, a murder mystery with Saoirse Ronan and Sam Rockwell, and His Dark Materials.
In July 2024, Clifford starred as journalist Chloe Slack in Time of the Week, a BBC Radio 4 comedy series. In March 2025, Clifford was nominated in the BBC Audio Drama Awards under Best Comedy Performance for her role in the show. The series returned for a second series in December 2025 to January 2026.
In 2024, Clifford starred in series two of the Channel 4 comedy Everyone Else Burns as Maude. In the series, Maude, a new member of the Order, tries to tempt father and husband David away from his wife Fiona. The Guardian said that this storyline was "a reminder of why this style of sitcom fell out of fashion" and that "As a character and plot device, Maude – who has no intelligible backstory – feels hollow".
In 2025, Clifford led the cast of mockumentary Lady, which was eventually released in August 2026.
In September 2025, it was announced Clifford had joined the cast of BBC detective series Ludwig, playing local MP Joanne Kemper in the second series.
