Her first stage appearance was at the Open Air Theatre, Regent's Park in 1953. She also appeared on-stage with Laurence Olivier, John Thaw and James Bolam in Semi-Detached (1962) by David Turner.

Among her accomplishments are the creation of two television series – along with Jean Marsh she created the concept for an original television series, titled Behind the Green Baize Door, which became the award-winning ITV series Upstairs, Downstairs (1971–75). Marsh played maid Rose for the duration of the series but Atkins was unable to accept a part due to stage commitments. The same team was also responsible for the BBC series The House of Eliott (1991–93).

As an actress her television work has included Three Sisters (1970), A Midsummer Night's Dream (1971), The Lady from the Sea (1974), Electra (1974), the villainess “Vanity Fair” in Dornford Yates' She Fell Among Thieves (1977), Sons and Lovers (1981), Oliver Twist (1982), Smiley's People (1982),Titus Andronicus (1985), The Burston Rebellion (1985), A Better Class of Person (1985), Roman Holiday (1987), The Lost Language of Cranes (1991), Cold Comfort Farm (1995), Talking Heads (1998), Madame Bovary (2000), David Copperfield (2000), Wit (2001) and Bertie and Elizabeth (2002).

Atkins has regularly returned to the life and work of Virginia Woolf for professional inspiration. She has played the writer on stage (A Room of One's Own and Vita and Virginia, winning the Drama Desk Award for Outstanding One-Person Show for the former) and screen (the 1990 television version of Room); she also provided the screenplay for the 1997 film adaptation of Woolf's novel Mrs. Dalloway – starring Vanessa Redgrave (her stage costar in Vita and Virginia) – and made a cameo appearance in the 2002 film version of Michael Cunningham's Woolf-themed novel The Hours.

Her other films include I Don't Want to Be Born (1975), Equus (1977), The Dresser (1983), Wolf (1994), Jack and Sarah (1995), Gosford Park (2001), Cold Mountain (2003), Vanity Fair (2004) and Ask the Dust (2006).

She has appeared in countless stage productions in and around London, including A Delicate Balance (1997), Cymbeline (1988), Honour (2003), John Gabriel Borkman (1996), Mountain Language (1988), The Night of the Iguana (1992), The Unexpected Man (1998) and The Birthday Party (2005).

Atkins has appeared on Broadway many times as well, scoring four Tony nominations as Best Actress in a Play. Her debut was in 1966, in Frank Marcus' The Killing of Sister George. Next was the Russian play The Promise (which closed after less than a month in 1967). In 1972's premiere of Robert Bolt's Vivat! Vivat Regina!, she played Elizabeth I to Claire Bloom's Mary, Queen of Scots. The Scandinavian novelty The Night of the Tribades barely ran for two weeks in 1977. A bit more successful were 1995's new version of Jean Cocteau's Indiscretions , directed by Sean Mathias (which co-starred Kathleen Turner and Broadway debutant Jude Law) and 2004's The Retreat from Moscow, William Nicholson's play about a marriage in ruins, with co-stars John Lithgow and Ben Chaplin.

In January 2006, she took over the lead role in the Broadway production of John Patrick Shanley's Pulitzer-prize winning play Doubt also featuring Ron Eldard and Jena Malone. Her off-Broadway work has included A Room of One's Own (1991) and The Unexpected Man (2001).

In the autumn of 2007, she co-starred with Judi Dench and Michael Gambon in the BBC1 drama series Cranford playing the central role of Miss Deborah Jenkyns. This performance earned her the 2008 BAFTA Award for best actress, as well as the Emmy Award.²

She returned to London's West End in January 2008 to play Mrs Rafi in Edward Bond's The Sea at the Theatre Royal, Haymarket. The play closed in April 2008. Later in 2008, she appeared at the Vaudeville Theatre in The Female of the Species, a play which outraged the feminist Germaine Greer because of its connection with an incident in her life. The play was, however, generally very well received, with The Sunday Telegraph reviewer Tim Walker giving it five stars and describing it as “great theatre.”

Atkins was created a Commander of the British Empire (CBE) in 1990, and raised to Dame Commander (DBE) in 2001. In 2008 Atkins signed onto the 2009 dark comedy, Wild Target, with such actors as Bill Nighy, Emily Blunt and Rupert Grint. She will be playing Nighy's mother, Louisa.

She recently played the evil Nurse Edwina Kenchington in the BBC Two sitcom Psychoville starring Dawn French. Atkins replaced Vanessa Redgrave as Eleanor of Aquitaine in the blockbuster movie Robin Hood starring Russell Crowe, which was released in the UK in May 2010.

Atkins and Jean Marsh, creators of the original 1970s series of Upstairs Downstairs, are among the cast of a new BBC adaptation, to be shown over the winter of 2010/11. The new series will be set in 1936. Marsh will again play Rose while Atkins has been cast as the redoubtable Lady Maud Holland.