Nelligan attended South Secondary School in London, Ontario then studied at the University of Toronto but did not graduate. Instead, she switched to studies at the Central School of Speech and Drama in London, United Kingdom. In 1973 she made her professional stage debut plus she appeared in a regular role on the British television series The Onedin Line. Her classical training saw her appear opposite Anthony Hopkins in the televised 1975 play, The Arcata Promise followed by the televised theatrical version of The Count of Monte Cristo that featured an all-star cast of British and American actors. That same year her first feature-length film The Romantic Englishwoman was released. In 1978 she was part of the BBC Television Shakespeare productions, and in 1979 she was the female lead with Frank Langella and Lord Sir Laurence Olivier in Dracula.

In 1981, she starred opposite Donald Sutherland in Eye of the Needle, a wartime espionage thriller based on the Ken Follett best-selling novel. Two years later, Nelligan moved to New York City where she earned four Tony Award "Best Actress" nominations between 1983 and 1989 from the five Broadway plays she appeared in. For her performance in the 1991 film, The Prince of Tides, she was nominated for the Academy Award for Best Supporting Actress. Between 1990 and 2004 she was nominated for five Gemini Awards for her performances on Canadian television mini-series and films.

Kate Nelligan has appeared in more than fifty feature-length or made-for-television films and on the stage in numerous plays. She returned to Broadway in 1997 and continues to appear in film.

Award wins:

BAFTA Award for Best Actress in a Supporting Role for Frankie and Johnny (1991) Genie Award for Best Actress in a Supporting Role for Margaret's Museum (1995) Award nominations: