While still in Texas, Zellweger appeared in several films. She appeared in A Taste for Killing (1992) as Mary Lou, then had a minor role in ABC TV mini series named Murder in the Heartland (1993). The following year, she appeared in Reality Bites (1994), the directorial debut of Ben Stiller, and in the biopic film 8 Seconds, directed by John G. Avildsen. Zellweger's first main part in a movie came with the 1994 horror movie Return of the Texas Chainsaw Massacre, in which she acted alongside Matthew McConaughey. She played Jenny, a teenager who leaves a prom early with three friends and ended up getting into a car accident, which leads to their meeting a murderous family. Her next movie was Love and a .45 (1994), in which she played the role of Starlene Cheatham, a woman who plans a robbery with her boyfriend. The performance earned her an Independent Spirit Award for Best Debut Performance. She subsequently moved to Los Angeles to pursue a career in acting, winning roles in the films Empire Records (1995) and The Whole Wide World (1996). Zellweger first became widely known to audiences around the world with her role in Jerry Maguire (1996), where she played the romantic interest of Tom Cruise's character. She won the role over Mira Sorvino and Marisa Tomei. Since then, Zellweger has won acclaim in roles such as One True Thing (1998) opposite William Hurt and Meryl Streep, and in Neil LaBute's Nurse Betty opposite Morgan Freeman. The role garnered the actress her first of three Golden Globe Awards, but she was in the bathroom when future co-star Hugh Grant announced her name. Zellweger later protested: "I had lipstick on my teeth!"

In 2001, Zellweger gained the prized lead role as Bridget Jones, playing alongside Hugh Grant and Colin Firth, in the British romantic comedy film Bridget Jones's Diary, a film that is based on the 1996 novel Bridget Jones's Diary by Helen Fielding, amid much controversy since she was neither British nor overweight. During casting Zellweger was told she was too skinny to play the chubby Bridget, so she very quickly embarked on gaining the required weight and learned an English accent. She gained 20 pounds in order to complete her transformation to Bridget Jones. Her dramatic weight fluctuations became the subject of much media interest. Her performance as Bridget received praise from critics, with Stephen Holden of The New York Times commenting, "Ms. Zellweger accomplishes the small miracle of making Bridget both entirely endearing and utterly real." Along with receiving voice coaching to fine-tune her English accent, part of Zellweger's preparations involved spending three weeks working undercover in a "work experience placement" for British publishing firm Picador in Victoria, London. As a result of her considerable efforts to effect author Helen Fielding's character, Zellweger caught the attention of the Academy of Motion Picture Arts and Sciences, and received her first Best Actress Academy Award nomination.

In 2002, she starred with Michelle Pfeiffer in White Oleander. The same year, she appeared as "Roxie Hart" in the critically-acclaimed musical film Chicago, directed by Rob Marshall, co-starring Catherine Zeta Jones, Richard Gere, Queen Latifah, and John C. Reilly. The movie received an Academy Award for Best Picture, and Zellweger received positive reviews from the critics. The SFGate commented, "Zellweger is a joy to watch, with marvelous comic timing and, in her stage numbers, a commanding presence." The Washington Post noted that even though Zellweger couldn't dance well in real life, the audience "wouldn't know it from this movie, in which she dances up a storm." As a result, she earned her second Academy Award nomination as Best Actress, as well as the Screen Actors Guild and Golden Globe Award.

In 2004, Zellweger received an Academy Award, this time as Best Supporting Actress in Anthony Minghella's Cold Mountain opposite Jude Law and Nicole Kidman. Zellweger has since starred in the sequel to Bridget Jones's Diary in Bridget Jones: The Edge of Reason, lent her voice to the DreamWorks animated features Shark Tale and Bee Movie, and starred in the 2005 Ron Howard film Cinderella Man opposite Russell Crowe and Paul Giamatti. On May 24, 2005, Zellweger received her star on the Hollywood Walk of Fame. She produced and appeared in Miss Potter, based on the life story of acclaimed author Beatrix Potter, with Emily Watson and Ewan McGregor, released in December 2006. In 2008, she starred in Appaloosa and the period comedy Leatherheads with fellow Oscar-winner George Clooney and John Krasinski (from The Office).

In 2008 she has been producing a film starring Harry Connick, Jr., about the true story of Dr. Denny Slamon. The film, called Living Proof, premiered in October 2008 on Lifetime Television. Craig Zadan and Neil Meron is also producing. It has been confirmed that she will star along side Chris Noth in the feature film My One and Only, due for release in 2009. The film is a 1950s-set comedy in which the glamorous "Anne Deveraux" (played by Zellweger) embarks on a drive down the Eastern Seaboard in a quixotic search for a wealthy man to fund a new life for her and her sons. StudioCanal and Alain Goldman's Legende are currently developing the next film from La Vie En Rose director Olivier Dahan entitled My Own Love Song. StudioCanal has confirmed that Renee Zellweger as well as Forest Whitaker are attached to the project.

• My Own Love Song (2009) (filming)
• My One and Only (2009) (post-production) .... Anne Deveraux
• Case 39 (2009) (completed) .... Emily Jenkins
  
• New in Town (2009) .... Lucy Hill
• Appaloosa (2008) .... Allison French
• Leatherheads (2008) .... Lexie Littleton
  ... aka Ein Verlockendes Spiel (Germany)
• Bee Movie (2007) (voice) .... Vanessa Bloome
• Miss Potter (2006) .... Beatrix Potter
• Cinderella Man (2005) .... Mae Braddock
• Bridget Jones Interviews Colin Firth (2005) (V) (uncredited) .... Bridget Jones
• Bridget Jones: The Edge of Reason (2004) .... Bridget Jones
  ... aka Bridget Jones - Am Rande des Wahnsinns (Germany)
  ... aka Bridget Jones - L'age 2 raison (France: DVD box title)
  ... aka Bridget Jones 2 (UK: informal title)
  ... aka Bridget Jones: L'âge de raison (France)
• Shark Tale (2004) (voice) .... Angie
• Cold Mountain (2003) .... Ruby Thewes
• Down with Love (2003) .... Barbara Novak
  ... aka Down with Love - Zum Teufel mit der Liebe! (Germany)
• Chicago (2002) .... Roxie Hart
  ... aka Chicago (Germany)
• White Oleander (2002) .... Claire Richards
  ... aka Weißer Oleander (Germany)
• Bridget Jones's Diary (2001) .... Bridget Jones
  ... aka Bridget Jones (UK: informal title)
  ... aka Journal de Bridget Jones, Le (France)
• "King of the Hill" .... Tammy Duvall (1 episode, 2001)
       - Ho, Yeah! (2001) TV episode (voice) .... Tammy Duvall
• Me, Myself & Irene (2000) .... Irene
• Nurse Betty (2000) .... Betty Sizemore