Annis began acting professionally in her teens, and made her film debut in "The Cat Gang" (1959). Her first major film role was as Elizabeth Taylor's handmaiden in "Cleopatra" (1963), in which she was cast at the age of 16 while still studying Russian ballet. Her big break was as one of the leads in the 1965 West End stage musical "Passion Flower Hotel". She played Estella in a television adaptation of "Great Expectations" (1967) and presented children's television programmes. She garnered attention for her performance as Lady Macbeth in Roman Polanski's film version of "Macbeth" (1971) in which she performs the sleepwalking soliloquy nude. The critic Kenneth Tynan was present when the scene was shot:"Francesca does it very sportingly and with no fuss ... though of course the set is closed, great curtains are drawn around the acting area ... and the wardrobe mistress rushes to cover Francesca with a dressing gown the instant Roman says, 'Cut'".