Natasha Richardson's first feature film, playing Mary Shelley in Ken Russell's Gothic, brought her to the attention of Paul Schrader, who then cast her in the highly acclaimed title role of Patty Hearst. Since then, she has achieved notable success in a number of feature films including A Month in the Country directed by Pat O'Connor, Roland Joffe's Fat Man and Little Boy starring Paul Newman and John Cusack, The Favour, the Watch and the Very Big Fish with Bob Hoskins and Jeff Goldblum, and Volker Schlondorf's The Handmaid's Tale co-starring Robert Duvall, Aidan Quinn and Faye Dunaway. She worked for Schrader again in The Comfort of Strangers alongside Rupert Everett, Helen Mirren and Christopher Walken, which brought her the London Evening Standard Award for Best Actress. She also starred in Widow's Peak with Mia Farrow and Joan Plowright (Best Actress Award at the 1994 Karlovy Vary Festival), Nell co-starring Jodie Foster and Liam Neeson, and The Parent Trap, Blow Dry, Waking Up in Reno and Chelsea Walls, directed by Ethan Hawke.

Richardson trained in London at the Central School of Speech and Drama. Her classical experience began with the roles of Helena in A Midsummer's Night's Dream, Ophelia in Hamlet at the Young Vic, and Nina in The Seagull, opposite her mother, Vanessa Redgrave, and Jonathan Pryce, (London Drama Critics: Most promising newcomer). Her other highly acclaimed stage performances include Tracey Lord in Richard Eyre's musical High Society, and the title role in Anna Christie, first in London (London Drama Critics' Best Actress) and then on Broadway, co-starring her future husband Liam Neeson (Tony nomination Best Actress in a Play, Theatre World Award for Outstanding Debut, Outer Critics Circle Outstanding debut of an Actress, and Drama Desk nomination for Best Actress). In 1998, she starred on Broadway as Sally Bowles in Sam Mendes' production of Cabaret (Tony Award, Drama Desk, Drama League and Outer Critics Awards for Best Actress in a Musical). A year later she portrayed Anna in the Broadway production of Patrick Marber's Tony nominated drama Closer.

Richardson's television credits include Ibsen's Ghosts with Judi Dench, Michael Gambon and Kenneth Branagh, Hostages, for HBO, the TV film of Tennessee Williams' Suddenly Last Summer for the BBC, with Maggie Smith and Rob Lowe. She starred as Zelda Fitzgerald in the TNT movie, Zelda co-starring Timothy Hutton and directed by Pat O'Connor (Cable Ace nomination for Best Actress). She also starred as Ruth Gruber in the CBS miniseries Haven, based on Ms. Gruber's autobiography.