Sybil Thorndike was born in Gainsborough, Lincolnshire, to Arthur Thorndike and Agnes Macdonald. Her father was a Canon of Rochester Cathedral. She was educated at Rochester Grammar School for Girls, and first trained as a classical pianist, making weekly visits to London for music lessons at the Guildhall School of Music and Drama. Her childhood home in Rochester has been renamed after her. She gave her first public performance as a pianist at the age of 11, but in 1899 was forced to give up playing owing to piano cramp. At the instigation of her brother, the author Russell Thorndike, she then trained as an actress. At the age of 21 she was offered her first professional contract: a tour of the United States with the actor-manager Ben Greet’s company. She made her first stage appearance in Greet’s 1904 production of Shakespeare’s The Merry Wives of Windsor. She went on to tour the U.S. in Shakespearean repertory for four years, playing some 112 roles. In 1908, she was spotted by the playwright George Bernard Shaw when she understudied the leading role of Candida in a tour directed by Shaw himself. There she also met her future husband, Lewis Casson. They were married in December 1908, and had four children: John (1909–1999), Christopher (1912–1996), Mary (1914–2009), and Ann (1915–1990). She was survived by four children and a number of grandchildren and great-grandchildren when she died. She joined Annie Horniman’s company in Manchester (1908–09 and 1911–13), went to Broadway in 1910, and then joined the Old Vic Company in London (1914–18), playing leading roles in Shakespeare and in other classic plays. After the war, she played Hecuba in Euripides The Trojan Women (1919–20), then from 1920–22 Thorndike and her husband starred in a British version of France’s Grand Guignol directed by Jose Levy.

She returned to the stage in the title role of George Bernard Shaw’s Saint Joan in 1924, which had been written with her specifically in mind. The production was a huge success, and was revived repeatedly until her final performance in the role in 1941. In 1927, Thorndike appeared in a short film of the cathedral scene from Saint Joan made in the DeForest Phonofilm sound-on-film process. Both Thorndike and Casson were active members of the Labour Party, and held strong left-wing views. Even when the 1926 General Strike stopped the first run of Saint Joan, they both still supported the strikers. She was made a Dame Commander of the Order of the British Empire in 1931. As a pacifist, Thorndike was a member of the Peace Pledge Union and gave readings for its benefit. During World War II, Thorndike and her husband toured in Shakespearean productions on behalf of the Council For the Encouragement of the Arts, before joining Laurence Olivier and Ralph Richardson in the Old Vic season at the New Theatre in 1944.  At the end of World War Two, it was discovered that Thorndike was on “The Black Book” or Sonderfahndungsliste G.B. list of Britons who were to be arrested in the event of a Nazi invasion of Britain. She continued to have success in such plays as N. C. Hunter’s Waters of the Moon at the Haymarket in 1951–52. She also undertook tours of Australia and South Africa, before playing again with Olivier in Uncle Vanya at Chichester in 1962. She made her farewell appearance with her husband in a London revival of Arsenic and Old Lace at the Vaudeville Theatre in 1966. Her last stage performance was at the Thorndike Theatre in Leatherhead, Surrey, in There Was an Old Woman in 1969, the year Lewis Casson died. Her final acting appearance was in a TV drama The Great Inimitable Mr. Dickens, with Anthony Hopkins in 1970. The same year she was made a Companion of Honour. She and her husband (who was knighted in 1945) were one of the few couples who both held titles in their own right. She had also been awarded an honorary degree from Manchester University in 1922, and an honorary D.Litt from Oxford University in 1966. Dame Sybil’s ashes are buried in Westminster Abbey.