Tyzack married Mathematician Alan Stephenson in 1958 and together they had one son, Matthew.

Tyzack was noted for her classical stage roles, having joined the Royal Shakespeare Company to play Vassilissa in Maxim Gorky's The Lower Depths in 1962, and had major roles in their 1972 Roman Season as Volumnia in Coriolanus, Portia in Julius Caesar and Tamora in Titus Andronicus. She appeared in another Gorky play, as Maria Lvovna in Summerfolk RSC 1974. In the late 1970s she spent three years on stage at Stratford, Ontario, where she played Mrs Alving in Ibsen's Ghosts, Queen Margaret in Richard III and the Countess of Roussillon in All's Well That Ends Well. She played the Countess again for the Royal Shakespeare Company on Broadway in 1983.

However, it was as a television Actress that Tyzack became a household name. She is remembered for her leading roles in BBC television productions. She came to notice as Winifred, Soames's sister, in the well received BBC adaptation of Galsworthy's The Forsyte Saga in 1967, a series shown internationally. Tyzack played Queen Anne in The First Churchills; Bette in Cousin Bette; and Antonia, mother of the Emperor Claudius, in I, Claudius. She also played Clothilde Bradbury-Scott in the BBC adaptation of the Agatha Christie story Nemesis in 1987.

Tyzack was appointed Officer of the Order of the British Empire (OBE) in the 1970 Birthday Honours and Commander of the Order of the British Empire (CBE) in the 2010 New Year Honours, both for services to drama.

She received an Olivier Award in 1982 for the National Theatre revival of Who's Afraid of Virginia Woolf? in which she played Martha, replacing Joan Plowright who was ill, and a Tony award in 1990 for the play Lettice and Lovage, in which she appeared in both the London and Broadway productions opposite Dame Maggie Smith. The American Actors' Equity initially refused permission for Tyzack to join the New York production, but Smith refused to appear without Tyzack because of the "onstage chemistry" she believed the two women had created in their roles. In 1994 she played Sybil Birling in the Royal National Theatre production of An Inspector Calls. In 2008, she was acclaimed for her portrayal of Mrs St Maugham in a revival of Enid Bagnold's The Chalk Garden at the Donmar Warehouse, London, for which she won the Best Actress award in the Critics' Circle Theatre Awards and the Laurence Olivier Award for Best Actress in 2009. In 2009, she appeared alongside Helen Mirren in Phedre at the Royal National Theatre.

She appeared in two films directed by Stanley Kubrick: 2001: A Space Odyssey (1968) and A Clockwork Orange (1971). Tyzack also appeared in Ring of Spies (1964), The Whisperers (1967), A Touch of Love (1969), The Legacy (1978), The Quatermass Conclusion (1979), Mr. Love (1985), Prick Up Your Ears (1987), The King's Whore (1990), Mrs Dalloway (1997), Bright Young Things (2003), and the Woody Allen films Match Point (2005) and Scoop (2006).

Tyzack died on 25 June 2011 after a short illness. She died at her home with her family by her side. Her family told the Daily Mail that Tyzack had faced her illness with "the strength, courage, dignity and even humour with which she lived her life."