With her big blue eyes and pronounced cheek bones which can be adapted for sympathy or stern menace, Hickson made her London stage debut in "The Tragic Muse" (1928). It was nearly a decade before she first stepped before the cameras in "Love From a Stranger" (1937), based, as much of her future work would be, on an Agatha Christie story. Film work remained rather sporadic, however, until she began working for John and Roy Boulting in 1948 with "The Guinea Pig". Hickson began playing small roles, often landladies or parents. She was the proprietor whose tenant was a German spy in "The Man Who Never Was" (1955) and the mother in "Carry On, Admiral" (1957). Hickson scored critical raves playing an uproariously funny drunken maid in "Upstairs and Downstairs" (1961) and also for playing a grandmotherly type in both the 1967 stage and 1972 film version of "A Day in the Death of Joe Egg" (The film was actually shot in 1970, but held for release for two years.) Hickson played the bookshop lady eyeing the young lovers in "Friends" (1971), and was Aunt Agatha to Faye Dunaway's "The Wicked Lady" (1983). Her film continued well into the 90s, with roles as the haughty Duchess of Marlborough in "King of the Wind" (1990), and her final screen appearance in "Century" (1993).

Hickson had been a regular on several British TV series over the years. She was the receptionist in the anthology series "The Royalty" (BBC, 1957-58), set in a hotel. In "Our Man at St. Mark's" (BBC, 1963-65), Hickson was the faithful housekeeper to a county vicar (played first by Leslie Stephens and later Donald Sinden). She continued to be active on TV after the age of 70, portraying Miss Havisham in 1982 BBC miniseries remake of "Great Expectations" followed by her turns as Miss Marple. Over the years, she also continued to make stage appearances, scoring a triumph on Broadway reprising her London stage role in the 1978 Broadway production of "Bedroom Farce". Paired with fellow veteran Michael Gough, Hickson won a Tony Award for her performance.