Witty and wise, this contemporary family drama revolves around Amy Mitchell (Mila Kunis), a married woman in the Chicago suburbs with two children, Jane (Oona Laurence) and Dylan (Emjay Anthony), who feels overworked and overcommitted. She works as a sales rep for a 'hip' coffee company, prepares healthful, hand-packed lunches for her children, does most of their homework, goes to all of their extracurricular activities, and is active in her school's PTA, run by the domineering Gwendolyn James (Christina Applegate) and her cronies, Stacy (Jada Pinkett Smith) and Vicky (Annie Mumolo).
When she catches her husband Mike (David Walton) cheating on her with a camgirl, Amy kicks him out and attempts to keep everything together.
After a particularly stressful day, Amy publicly quits the PTA in response to Gwendolyn's overzealous bake sale plans. At a nearby bar, Amy meets Carla (Kathryn Hahn), a laid-back, sexually active single mom, and Kiki (Kristen Bell), a stay-at-home mom of four who adores Amy's dissent from Gwendolyn. Amy and Carla are irritated to discover that Kiki's husband is domineering and expects her to take care of all the kids and the house with no assistance whatsoever, while Amy and Kiki are disturbed at Carla's very hands-off approach to parenting.
The trio embark on an all-night bender that inspires Amy to loosen up with her kids: she takes them for rides in Mike's classic car, gets them lunch from Arby's, forces Dylan to fend for himself to prevent him from being lazy and entitled, and takes the overachieving and constantly stressed Jane for a spa day. Amy herself decides to start dating but finds herself inexperienced due to her early marriage and motherhood.
She ultimately ends up striking a connection with Jessie (Jay Hernandez), a handsome widower at the school who's had a crush on her.
After Amy brings store-bought donut holes to the bake sale, she draws the ire of Gwendolyn, who uses her PTA authority to get Jane benched from the soccer team. Amy is angered, and decides to run for PTA president in opposition to Gwendolyn.
A meet-and-greet at Amy's home draws only one visitor, who informs them that Gwendolyn has launched a rival party at her own house, catered by Martha Stewart. In spite of this, the other moms, and Martha, swiftly abandon Gwendolyn's party when it becomes clear that she intends to lecture them all evening, leading to a successful party at Amy's house.
Gwendolyn responds by putting drugs in Jane's locker, which gets her kicked out of all extracurricular activities. Jane and Dylan both go to stay with Mike (who has agreed to an amicable divorce) in response to what they see as Amy's failure as a mom. Amy loses her job because her boss refuses to understand her reasons for taking time off.
A despondent Amy stays home during the PTA election but is roused into action by Carla and Kiki, who finally stands up to her husband and orders him to deal with everything alone until the meeting is over. At the event, Amy gives an inspiring speech about how all the moms are overworked and that they need to take time off, do fewer and less stressful events, and most importantly, allow themselves to make mistakes.
Amy wins by a landslide and eventually winds up comforting a devastated Gwendolyn, who reveals that her life is not perfect like she claims it is and that being in charge of the PTA was her only way to take her anger out on the problems she is facing.
Some weeks later, Amy's approach has led to positive changes: Jane has been reinstated to the soccer team and is stressing out less, Dylan is actually applying himself, Kiki makes her husband help out with taking care of their kids, Carla is more responsible and hands-on, and all of the other moms, including Stacy and Vicky, are feeling more energized. Amy herself has gotten her job back with much better compensation after her boss sees how much he had taken her for granted, and she continues to see Jessie. Gwendolyn invites Amy, Carla, and Kiki for a day of fun on her husband's private jet.
The ending credits play over the cast interviewing their real-life moms.