[13] In 1986, her academic paper, "The Karankawas and Their Roots", won third place in the first-ever Houston Post High School Natural Science Essay Contest.

[18] Also while in college, she did "a bit part ... as a local hire" in the Austin-filmed horror-comedy film My Boyfriend's Back, playing "the girl in the beauty shop, maybe two lines.

[22] Her first main role in a movie came with the 1995 horror film The Return of the Texas Chainsaw Massacre, alongside Matthew McConaughey, playing a teenager who leaves a prom early with three friends who get into a car accident, which leads to their meeting a murderous family, led by the iconic Leatherface.

[11] While the film went unnoticed,[23] Joe Leydon for Variety magazine lauded Zellweger, calling her "the most formidable scream queen since Jamie Lee Curtis went legit.

Although the film received a limited release in theaters,[25] Marc Savlov of Austin Chronicle applauded the main cast saying they were "all excellent in their roles" and noted that "Zellweger's character – all squeals and caged sexuality – seems a bit too close to Juliette Lewis' Mallory Knox (of Natural Born Killers) to be as fresh as it should be".

[11] Rotten Tomatoes' consensus was: "Despite a terrific soundtrack and a strong early performance from Renee Zellweger, Empire Records is mostly a silly and predictable teen dramedy.

"[27] Zellweger came to wider recognition through her role in Jerry Maguire (1996), playing a single mother and the romantic interest of a glossy sports agent (Tom Cruise).

She played a woman, based on author Anna Quindlen, forced to put her life on hold in order to care for her mother, who is dying of cancer.

[44] In the black comedy Nurse Betty (2000), directed by Neil LaBute and starring Morgan Freeman,[11] Zellweger played a Kansas waitress who suffers a nervous breakdown after witnessing her husband's murder.

[48] She won her first Golden Globe Award for Best Actress – Motion Picture Musical or Comedy, but she was in the bathroom when future co-star Hugh Grant announced her name.

[11] During casting, Zellweger was told she was too thin to play the cherubic, chain-smoking Bridget, so she quickly embarked on gaining the required weight (20 pounds) and learning to speak in an English accent while she smoked herbal cigarettes.

[11][51] Her portrayal of Jones led Stephen Holden of The New York Times to comment, "Ms. Zellweger accomplishes the small miracle of making Bridget both entirely endearing and utterly real.

[53] She also portrayed Roxie Hart in the 2002 musical film Chicago, directed by Rob Marshall and co-starring Catherine Zeta-Jones, Richard Gere, Queen Latifah, and John C. Reilly.

[54][55] Writing for The Daily Telegraph, Tim Robey labeled Chicago the "best screen musical [since 1972's Cabaret]",[56] and the San Francisco Chronicle commented, "Zellweger is a joy to watch, with marvelous comic timing and, in her stage numbers, a commanding presence".

[69] In 2005, she played the wife of world heavyweight boxing champion James J. Braddock in Ron Howard's drama Cinderella Man, opposite Russell Crowe and Paul Giamatti.

[78] With George Clooney in his directorial venture, the period comedy Leatherheads (2008), about the early years of professional American football, Zellweger portrayed a Chicago Tribune newspaper reporter.

[79][80] The film received largely mixed reviews and made US$13.5 million in its opening weekend, described as "disappointing" by website Box Office Mojo.

[89][90] Peter Bradshaw of The Guardian stated that her "rabbity, dimply pout – surely the strangest facial expression in Hollywood – simpers and twitches out of the screen in this moderate girly flick that adheres with almost religious fanaticism to the feelgood romcom handbook".

[91] In 2009, she also provided her voice for a supporting character in DreamWorks' animated film Monsters vs. Aliens,[92] and starred as the mother of actor George Hamilton in the comedy My One and Only,[93] which despite being distributed for a limited release to certain parts of the United States only.

[97][98] It was universally panned by critics and only earned US$5.3 million in its opening weekend,[99][100] leading Indiewire to write that Zellweger "faces an [u]ncertain [f]uture" as she was in "an unforgiving industry that doles out few juicy roles for women over 40.

[107][108] In 2013, Zellweger co-created and executive produced Cinnamon Girl, an original drama series set in the Hollywood movie and music scenes of the late 1960s and early 1970s, but the Lifetime network passed on the pilot.

[112][113] Village Voice found the movie to be "the warmest and most satisfying of the series" and concluded that Zellweger's "wise, light-hearted performance anchors this happy reunion, a surprising and refreshing gift from a creative well that seemed to have run dry".

[114] In Same Kind of Different as Me (2017), a film adaptation of the autobiographical book by the same name, Zellweger starred with Djimon Hounsou, Olivia Holt and Jon Voight, as the wife of an art dealer whose struggling relationship is changed for the better by a homeless man.

The Wrap, nevertheless, remarked: "Zellweger, in fact, delivers a gentle, thoughtful, yet headstrong performance as the wife who digs in her heels to get human decency out of the people she cares for the most".

[124] Zoe Gahan of Vanity Fair found her "witty, sharp and devastating in the title role" and added that "it is hard to tell where Garland stops and Zellweger starts".

[125] Peter Travers of Rolling Stone opined, "Zellweger performs miracles playing Judy Garland: singing her heart out, baring her bruised soul and acting with a ferocity that ultimately rises to a state of grace.

[131] IndieWire's Ben Travers called her performance "exaggerated", while John Doyle of The Globe and Mail said that she "brings an equal amount of vinegary exuberance to the work".

[135] Zellweger often draws attention for her style at award ceremonies and red carpet events,[136] specifically for her frequent use of dresses designed by Carolina Herrera,[137][138][139][140] a close friend who has worked with the actress for over fifteen years after they met at a Costume Institute gala.

After Zellweger attended the 21st annual Elle Women in Hollywood Awards in October 2014, there was media and social commentary that she was hardly recognizable, which prompted speculation that she had undergone cosmetic surgery.

[160][161][162] In June 2021, Zellweger began dating English television presenter Ant Anstead whom she met filming Celebrity IOU: Joyride.