Weisz was born in London. Her father, George Weisz, is a Hungarian-born Jewish inventor whose family fled to England in order to escape Nazi persecution. Her mother, Edith, is a Vienna-born Austrian Catholic psychoanalyst and aspiring actress, who has Austrian Jewish and ¼ Italian Catholic ancestry. Weisz's family raised her Jewish.

Weisz read English at Trinity Hall, Cambridge. She graduated with a 2:1. During her college years she appeared in various student productions, co-founding a student drama group called Cambridge Talking Tongues, which went on to win a Guardian Student Drama Award at the Edinburgh Festival for an improvised piece called Slight Possession.


Her breakthrough role was that of Gilda in Welsh director Sean Mathias's 1995 West End revival of Noël Coward's 1933 play Design for Living at the Gielgud Theatre. Having already worked for television, Weisz started her cinema career in 1995 with Chain Reaction, then Bernardo Bertolucci's Stealing Beauty. She followed this work with more English films including Swept from the Sea, The Land Girls, and Michael Winterbottom's I Want You. Since then she has starred in a number of films including The Mummy (1999), About a Boy (2002), Runaway Jury (2003) and Constantine (2005). Her stage work includes the role of Catherine in a London production of Tennessee Williams' Suddenly Last Summer and Evelyn in Neil LaBute's The Shape of Things at the Almeida Theatre (also film).

In 2005, Weisz starred in The Constant Gardener, a film adaptation of a John le Carré thriller of the same title set in the slums of Kibera and Loiyangalani, Kenya. For this role, Weisz won the 2006 Academy Award for Best Supporting Actress, the 2006 Golden Globe for Best Supporting Actress, the 2006 Screen Actors Guild Award for Outstanding Performance by a Female Actor in a Supporting Role. She was nominated for her role at the BAFTA's but in the best actress category, she eventually lost to Reese Witherspoon.

In 2006, Weisz will star in The Fountain, written and directed by her fiancé, Darren Aronofsky. In the same year, she plans to star in a New York production of August Strindberg's Miss Julie, playing the titular role.