Having already worked for television, with parts in major UK series such as Inspector Morse (1993), Weisz started her cinema career in 1995 with Chain Reaction and then appeared in Bernardo Bertolucci's Stealing Beauty. She followed this work with more English films including My Summer with Des, Swept from the Sea, The Land Girls, and Michael Winterbottom's I Want You. Although she received favourable critical recognition for her work to this point, her breakout into wide audience recognition came from a popular serio-comic horror movie The Mummy, in which she played the lead female role alongside Brendan Fraser. She followed this up with two hits, The Mummy Returns (2001), which grossed higher than the original, and About a Boy (2002) with Hugh Grant. Since then, her other film work has included Runaway Jury (2003) and Constantine (2005).

In 2005, Weisz starred in Fernando Meirelles's 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 performance, Weisz won the 2006 Academy Award for Best Supporting Actress, the 2006 Golden Globe Award for Best Supporting Actress and the 2006 Screen Actors Guild Award for Outstanding Performance by a Female Actor in a Supporting Role. In her home country, she was recognised as a leading role for the film according to the nomination from the BAFTA awards and winnings from the London Critics Circle Film Awards and British Independent Film Awards.

The same year, she starred in The Fountain and also provided the voice for Saphira in the much-criticized film Eragon. Her 2008 films include the Wong Kar-wai-directed drama My Blueberry Nights (in which she played an "anti-Southern belle") and director Rian Johnson's upcoming The Brothers Bloom, in which she plays a wealthy American woman targeted by two con man brothers (Adrien Brody, Mark Ruffalo). She will also play the lead in the multi-million motion picture Agora, which is currently set to be released in 2009.

• Dirt Music (2009) (pre-production) .... Georgie Jutland
• The Lovely Bones (2009) (post-production) .... Abigail Salmon
• Agora (2009) (post-production) .... Hypatia
  
• The Brothers Bloom (2008) .... Penelope Stamp
• Definitely, Maybe (2008) .... Summer Hartley
  ... aka Un jour, peut-être (France)
• Fred Claus (2007) .... Wanda
• My Blueberry Nights (2007) .... Sue Lynne Copeland
• Eragon (2006) (voice) .... Saphira
• Eragon (2006) (VG) (voice) .... Saphira
  ... aka Eragon: The Game (International: English title: informal title)
• The Fountain (2006) .... Isabel / Izzi Creo
• The Constant Gardener (2005) .... Tessa Quayle
  ... aka Der Ewige Gärtner (Germany)
• Constantine (2005) .... Angela Dodson / Isabel Dodson
  ... aka Constantine (Germany)
• Envy (2004) .... Debbie Dingman
• Runaway Jury (2003) .... Marlee
• Confidence (2003) .... Lily
  ... aka Confidence: After Dark (UK)
  ... aka En toute confiance (Canada: French title)
• The Shape of Things (2003) .... Evelyn Ann Thompson
  ... aka Fausses apparences (France: TV title)
• About a Boy (2002) .... Rachel
  ... aka About a Boy oder: Der Tag der toten Ente (Germany)
  ... aka Pour un garçon (France)
• The Mummy Returns (2001) .... Evelyn Carnahan O'Connell / Princess Nefertiri
• Enemy at the Gates (2001) .... Tania Chernova
  ... aka Duell - Enemy at the Gates (Germany)
• Beautiful Creatures (2000) .... Petula
• This Is Not an Exit: The Fictional World of Bret Easton Ellis (2000) .... Lauren Hynde