Thompson was born in Paddington, London to Eric Thompson (an English actor known for narrating the television series The Magic Roundabout) and Phyllida Law (a Scottish actress). Her sister is actress Sophie Thompson.
Thompson went to Camden School for Girls and then read English Literature at Newnham College, Cambridge, where she was a member and vice-president of the Footlights comedy club. While there, Thompson dated Footlights member and future actor, Hugh Laurie. After completing her education, she came to fame with a leading role in the West End revival of the musical Me and My Girl, opposite Robert Lindsay, followed by the BBC serial drama, Fortunes of War.
Thompson's first major film role was in a romantic comedy, The Tall Guy (1989). Her career took a more serious turn with a series of critically acclaimed performances and films, beginning with 1992's Howards End (for which she received an Oscar for Best Actress), the part of Gareth Peirce, the lawyer for the Guildford Four, in 1993's In the Name of the Father, The Remains of the Day opposite Anthony Hopkins, and as the British painter Dora Carrington in the film Carrington (1995). She won her next Oscar in 1996, for Best Adapted Screenplay for her screenplay adaptation of Jane Austen's Sense and Sensibility, a film in which she also played the Oscar-nominated lead actress role. Consequently, Thompson is the first, and so far only, person to have won Oscars for both acting and writing; she has said that she keeps both of her award statues in her downstairs bathroom, citing embarrassment at placing them in a more prominent place.
One of Thompson's earliest television appearances was in 1984 alongside Stephen Fry and Hugh Laurie as guest stars on the sitcom The Young Ones. In 1988, she starred in and wrote the eponymous Thompson comedy sketch series for BBC1. Thompson's recent television work has included a starring role in the 2001 HBO drama Wit, in which she played a dying cancer victim, and 2003's Angels in America, playing multiple roles, including one of the titular angels. Her Emmy Award was as a guest star in a 1997 episode of the show Ellen; in the episode, she played a parody of herself. She also appeared in an episode of Cheers in 1992. Her character, Nanette "Nanny" Gee, was the host of a children's television program and Frasier Crane's first wife.
Most recently, Thompson appeared in supporting roles in films of a lighter nature, including her role as Sybill Trelawney in Harry Potter and the Prisoner of Azkaban (2004) and the comedy Love Actually (2003).
The film Nanny McPhee, written by Thompson, was first released in October 2005. Thompson has worked on the project for 9 years, having written the screenplay and starred, alongside her mother (who has a cameo appearance). In her most recent film, Stranger Than Fiction, she plays an author planning on killing her main character, who turns out to be a real person.
Whilst she was at Cambridge University, Thompson had a romantic relationship with her fellow student, actor Hugh Laurie, who was also a member of the Cambridge Footlights Revue, and now star of the hit show "House."
Thompson married Kenneth Branagh, with whom she appeared in Fortunes of War, on August 20, 1989. They appeared together several times, in hit films such as Dead Again, Henry V and Much Ado About Nothing, but were eventually divorced in October 1995.
In 2003, Thompson married actor Greg Wise (who starred with her in Sense and Sensibility) with whom she has a daughter, Gaia Romilly, born in 1999.
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