Atkinson made her television debut in the British series London's Burning, as Zoe, the girlfriend (later wife) of fireman Colin Parrish. She appeared in the series from 1991 to 1993. Her film debut came in the 1997 film Keep the Aspidistra Flying, which starred Helena Bonham Carter.

She has performed many shows at the Stephen Joseph Theatre with Alan Ayckbourn, including The Boy Who Fell Into a Book, in which she originated the role of the Queen in 1998.

In 1999, she played Jessie Bond in Topsy-Turvy, performing the song 'Three Little Maids From School Are We' with Shirley Henderson and Cathy Sara. Topsy-Turvy was nominated for four Academy Awards, winning two.

In 2002, Atkinson was nominated for Best Supporting Actress for her performance in Eden End as Lillian, by the Barclays Theatre Awards, an award recognising regional British theatre.

She played Mrs. MacGregor in the 2006 television film Housewife, 49, which won the BAFTA Award for Best Single Drama. In 2010 played Hannah Murray's mother in Chatroom and in 2013, she began playing Jane Sutton on the British series Call the Midwife.

In 2009 Atkinson played Vera in Just Between Our Selves by Alan Ayckbourn at Northampton's Royal & Derngate Theatre. In 2006 she played Nora in Epitaph for George Dillon at the Comedy Theatre and in 2007 the Woman in A Matter of Life and Death at the National Theatre. In 2003 she played Marie in the Royal Shakespeare Company's production of Beauty and the Beast by Laurence Boswell.

Atkinson made her Broadway debut in the 2010 production of Brief Encounter, playing three roles (Dolly/Hermione/Beryl). This production was conceived originally with the Kneehigh Theatre Company (of which she is a member) and she stayed with the show when it moved to New York.