Flynn was born in Kansas City, Missouri and raised in midtown Kansas City's Coleman Highlands neighborhood. Both of her parents were professors at Metropolitan Community College–Penn Valley: her mother, Judith Ann (née Schieber), was a reading-comprehension professor, and her father, Edwin Matthew Flynn, was a film professor. She has an older brother, Travis, who is a railroad machinist. Her uncle is Jackson County Circuit Court Judge Robert Schieber. Flynn was "painfully shy" and found escape in reading and writing. Growing up, Flynn's father would take her to watch horror movies.
Flynn attended Bishop Miege High School and graduated in 1989. As a teenager, she worked odd jobs which required her to do things such as dress up as a giant "yogurt cone who wore a tuxedo."
She attended the University of Kansas, where she received her undergraduate degrees in English and journalism. She spent two years in California, writing for a trade magazine for human resources professionals, before moving to Chicago and attending Northwestern University for a master's degree at its Medill School of Journalism in 1997. Flynn initially wanted to work as a police reporter, but she chose to focus on her own writing, as she discovered she had "no aptitude" for police reporting.
After graduating from Northwestern, Flynn worked freelance briefly at U.S. News & World Report before being hired as a feature writer in 1998 at Entertainment Weekly. She was promoted to television critic and wrote about films but was laid off in December 2008.
She attributes her craft to her 15-some years in journalism. She said, "I could not have written a novel if I hadn't been a journalist first, because it taught me that there's no muse that's going to come down and bestow upon you the mood to write. You just have to do it. I'm definitely not precious."
Some critics have accused Flynn of misogyny due to the often unflattering depiction of female characters in her books. Flynn identifies as a feminist. She feels that feminism allows for women to be bad characters in literature. She states, "The one thing that really frustrates me is this idea that women are innately good, innately nurturing." Flynn also said people will dismiss "trampy, vampy, bitchy types – but there's still a big pushback against the idea that women can be just pragmatically evil, bad, and selfish". In 2015, Flynn explained her decision to write cruel female characters, saying, "I've grown quite weary of the spunky heroines, brave rape victims, soul-searching fashionistas that stock so many books. I particularly mourn the lack of female villains – good, potent female villains."
When Flynn was working for Entertainment Weekly, she was also writing novels during her free time. She has written three novels and one short story.Sharp Objects (2006) revolves around a serial killer in a Missouri town, and the reporter who has returned to her hometown from Chicago to cover the event. Themes include dysfunctional families, violence and self-harm. The book was partly inspired by Dennis Lehane's Mystic River. In 2007, the book was shortlisted for the Mystery Writers of America Edgar for Best First Novel by an American Writer, Crime Writers' Association Duncan Lawrie, CWA New Blood and Ian Fleming Steel Daggers, winning in the last two categories.
Dark Places (2009) is about a woman who investigates whether or not her incarcerated brother was truly responsible for the murder of their family in the 1980s, which happened when she was a child during the era of panic about Satanic ritual abuse. Dark Places was adapted into a 2015 feature film, written and directed by Gilles Paquet-Brenner. Flynn made a cameo appearance in the film.
Gone Girl (2012) was released in June 2012 and concerns a husband who searches for his wife, who disappeared on their fifth wedding anniversary, while he comes under police scrutiny as the prime suspect. Flynn wrote the script for a film adaptation of Gone Girl after 20th Century Fox purchased the film rights for $1.5 million. The film was directed by David Fincher and was released on October 3, 2014 to critical acclaim. The novel was No. 1 on the New York Times Hardcover Fiction Bestseller list for eight weeks. Culture writer Dave Itzkoff wrote that the novel was, excepting books in the Fifty Shades of Grey series, the biggest literary phenomenon of 2012. By the end of that year, Gone Girl had sold over two million copies in print and digital editions, according to the book's publisher.
The Grownup (2015) was released in 2015; it was originally published as a short story in the 2014 anthology Rogues, edited by George R. R. Martin and Gardner Dozois, under the title "What Do You Do?". The story is about a sex worker who becomes an aura reader and is then hired by a woman with a failing marriage and a disturbing step-son to purify her Victorian home. The story won an Edgar Award in 2015 for best short story.
Flynn was an avid reader of comic and graphic novels when she was a child. She collaborated with illustrator Dave Gibbons and wrote a comic book story called Masks. It is part of the anthology series Dark Horse Presents and was published by Dark Horse Comics in February 2015.
In February 2014, it was reported that Flynn will be writing the scripts for Utopia, an HBO drama series adapted from the acclaimed British series Utopia. The HBO series is to be directed and executive produced by David Fincher. As of July 2015 the project has been cancelled due to budget disputes between Fincher and HBO. Flynn will serve as executive producer and co-writer, alongside Marti Noxon, on the HBO adaptation of her novel Sharp Objects starring Amy Adams.
For her Gone Girl screenplay, Flynn was nominated for the Golden Globe, Writers Guild of America Award and BAFTA Award for Best Adapted Screenplay. Flynn and filmmaker Steve McQueen co-wrote a film adaption of the BBC series Widows. The film is set to star Viola Davis and will be released in 2018.
She married lawyer Brett Nolan in 2007 and they have two children. Their son Flynn was born in 2010 and their daughter Veronica was born August 6, 2014. They met through a grad school classmate at Northwestern, but did not start dating until she moved back to Chicago from New York City in her mid-30s. As of at least 2013, they reside in Chicago.