At 21, Diaz auditioned for The Mask, even though she had no previous acting experience, based on the recommendation of an agent for Elite who met the film's producers while they were searching for the female lead. After obtaining the lead female role, she immediately started acting lessons. Over the next three years, she won roles in low-budget, independent films, such as The Last Supper, Feeling Minnesota, and She's the One, preferring to feel her way effectively into the business. She then regained mainstream success with her roles in My Best Friend's Wedding and There's Something About Mary, a film for which she was nominated for a Golden Globe in the category of Best Actress - Musical or Comedy. She won critical acclaim for her performance in Being John Malkovich, which earned her Best Supporting Actress nominations at the Golden Globes, the BAFTA Awards, and the SAG Awards.

During the 1999-2000 period, Diaz starred in many films, such as Things You Can Tell Just by Looking at Her, A Life Less Ordinary, Any Given Sunday, and the hit adaptation of Charlie's Angels. In 2001, she won nominations for Best Supporting Actress at the Golden Globes, the SAG Awards, and the AFI Awards for Vanilla Sky, and also voiced Princess Fiona in Shrek, for which she earned $10 million. In 2003, Diaz received another Golden Globe nomination for Martin Scorsese's epic Gangs of New York, and became the third actress (after Wedding costar Julia Roberts and Reese Witherspoon) to earn $20 million for a role, receiving the sum for Charlie's Angels: Full Throttle. Her next film appearances were in Shrek 2, In Her Shoes, and The Holiday . During 2004 and early 2005, Diaz explored some of the planet's environmentally unique locations while discovering ways to help preserve them for the 10-episode MTV series Trippin' which featured numerous celebrities and friends of Diaz, such as Jessica Alba, Drew Barrymore, Mark Hoppus, Eva Mendes, and Justin Timberlake.

Diaz returned to the screen for Shrek the Third in 2007, in which she co-starred with her boyfriend Justin Timberlake. She was set to team up again with The Mask co-star Jim Carrey in the film Fun with Dick and Jane, but dropped out to star in In Her Shoes. She also appeared in the romantic comedy What Happens in Vegas, opposite Ashton Kutcher. She will also appear in Shrek 4 and is also set to star in The Box, a horror thriller in 2008 co-starring James Marsden. On July 7, 2007, Diaz participated at Live Earth in New York by introducing Bon Jovi and The Police. In 2007, People ranked her as the Best Dressed Female Celebrity. In August 2008, Forbes Magazine listed Diaz as the highest paid actress in Hollywood. She reportedly earned $50 million in the period of a year ending June 2008, for her roles in What Happens in Vegas and the Shrek films. She made a cameo on Saturday Night Live on February 15, 2009 with guest star Alec Baldwin as a cougar named Kiki Damore on a skit called "The Cougars' Den".

• Untitled James Mangold Project (2010) (announced) (rumored)
• Shrek Goes Fourth (2010) (post-production) (voice) .... Princess Fiona
  ... aka Shrek Goes Fourth: An IMAX 3D Experience (USA: IMAX version)
• The Box (2009/I) (completed) .... Norma Lewis
• My Sister's Keeper (2009) (completed) .... Sara Fitzgerald
  
• "Saturday Night Live" .... Kiki Deamore / ... (3 episodes, 2008-2009)
  ... aka "NBC's Saturday Night" (USA: complete title)
  ... aka "SNL 25" (USA: alternative title)
  ... aka "SNL" (USA: informal title)
  ... aka "Saturday Night Live '80" (USA: sixth season title)
  ... aka "Saturday Night" (USA: first season title)
       - Alec Baldwin/Jonas Brothers (2009) TV episode (uncredited) .... Various artists
       - James Franco/Kings of Leon (2008) TV episode (uncredited) .... Kiki Deamore
       - Ashton Kutcher/Gnarls Barkley (2008) TV episode (uncredited) .... Kiki Deamore
• What Happens in Vegas (2008) .... Joy McNally
• Shrek the Halls (2007) (TV) (voice) .... Princess Fiona
• Shrek the Third (2007) (voice) .... Princess Fiona
  ... aka Shrek 3 (Singapore: English title) (USA: working title)
  ... aka The Third (USA: promotional abbreviation)
• The Holiday (2006) .... Amanda Woods
• In Her Shoes (2005) .... Maggie
  ... aka In den Schuhen meiner Schwester (Germany)
• Far Far Away Idol (2004) (V) (voice) .... Fiona
• Shrek 2 (2004) (voice) .... Princess Fiona
• Charlie's Angels: Full Throttle (2003) .... Natalie Cook
• Shrek 4-D (2003) (voice) .... Princess Fiona
  ... aka Shrek 3-D (USA: DVD title)
• Gangs of New York (2002) .... Jenny Everdeane
• Minority Report (2002) (uncredited) .... Woman on Metro
• My Father's House (2002) .... The Girl
• The Sweetest Thing (2002) .... Christina Walters
• Vanilla Sky (2001) .... Julie Gianni
• Shrek (2001) (voice) .... Princess Fiona
• The Invisible Circus (2001) .... Faith
• Shrek in the Swamp Karaoke Dance Party (2001) (V) (singing voice) .... Princess Fiona
• Charlie's Angels (2000) .... Natalie Cook
  ... aka 3 Engel für Charlie (Germany)
• Things You Can Tell Just by Looking at Her (2000) .... Carol Faber (segment "Love Waits For Kathy")