She was born Sarah Kemble in Brecon, Brecknockshire, Wales, the eldest daughter of Roger Kemble, an actor-manager whose travelling company included most members of his family. Sarah's brothers, Charles Kemble, John Philip Kemble and Stephen Kemble were all actors. Her youngest sister, Ann Hatton, became a novelist.

Acting was only just becoming a respectable profession for a woman. In 1773, Sarah married William Siddons, another member of the company, and made her debut at Drury Lane two years later, in David Garrick's company as Portia in The Merchant of Venice. It was a disaster, and her contract was not renewed at the end of her first London season.

For the next six years she worked in provincial companies (in particular York and Bath), gradually building up a reputation, and her next Drury Lane appearance, on 10 October 1782, could not have been more different. She was an immediate sensation playing the title role in Garrick's adaptation of a play by Thomas Southerne, Isabella, or, The Fatal Marriage. It was the beginning of twenty years in which she was the undisputed queen of Drury Lane.

In 1802 she left Drury Lane and subsequently appeared from time to time on the stage of the rival establishment, Covent Garden. It was there, on 29 June 1812, that she gave perhaps the most extraordinary farewell performance in theatre history. She was playing her most famous role, Lady Macbeth, and the audience refused to allow the play to continue after the end of the sleepwalking scene. Eventually, after tumultuous applause from the pit, the curtain reopened and Mrs Siddons was discovered sitting in her own clothes and character - whereupon she made an emotional farewell speech to the audience lasting eight minutes.

Sarah Siddons died in 1831 in London and was interred there in Saint Mary's Cemetery at Paddington Green.