Weiner was born in DeRidder, Louisiana, where her father was stationed as an army physician. She (along with her younger sister and two brothers) eventually moved to in Simsbury, Connecticut, where she spent most of her childhood. Her parents divorced when she was 16, a topic that features in many of her novels. Her mother came out as a lesbian at age 55. Weiner was also influenced by her experience as one of "nine Jewish kids in her high school class of 400" at Simsbury High School. She entered college at the age of 17 and received her bachelor of arts summa cum laude in English from Princeton University in 1991, having studied with J. D. McClatchy, Ann Lauterbach, John McPhee, Toni Morrison, and Joyce Carol Oates.
After college, Weiner became a reporter for the Centre Daily Times, the daily newspaper of State College, Pennsylvania, where she managed the education beat and wrote a regular column, Generation XIII -- about the 13th generation following the American Revolution. After moving on to Kentucky's Lexington Herald-Leader and maintaining her "Generation XIII" column, obstensibly about Generation X, she next found a position with The Philadelphia Inquirer as a features reporter. She worked steadily as a journalist until publishing her first novel, Good in Bed, in 2001. Her second novel, In Her Shoes, published in 2002, was made into a film in 2005, and starred Cameron Diaz, Toni Collette and Shirley MacLaine. Weiner has written seven novels to date, all of which have Jewish protagonists. She has stated that she is a feminist.
Weiner has repeatedly defended the "Chick lit" label that is often attached to her novels.
In her blog on June 7, 2008, Weiner responds to an article on "Chick lit", a review by Curtis Sittenfeld of a Melissa Bank novel. Weiner deconstructs the Sittenfeld's review and states, "The more I think about the review, the more I think about the increasingly angry divide between ladies who write literature and chicks who write chick lit, the more it seems like a grown-up version of the smart versus pretty games of years ago; like so much jockeying for position in the cafeteria and mocking the girls who are nerdier/sluttier/stupider than you to make yourself feel more secure about your own place in the pecking order." In a follow-up interview with the San Francisco Chronicle on the Bank/Sittenfeld articles, Weiner commented, "I'd say this is a reaction against women gaining power and economic stature in the marketplace. Book sales are flat, chick lit sales are up. And that's scary to a lot of people. It's better for the establishment to slap it down, degrade it."