Carly (Cameron Diaz) has just started a relationship with Mark (Nikolaj Coster-Waldau), a man she hooked up with eight weeks prior. She is upset when Mark suddenly tells her he has to go out of town, but decides to go over to his house per advice from her father Frank (Don Johnson). Intending to seduce him while wearing a sexy outfit, she is horrified to meet Kate (Leslie Mann), who introduces herself as Mark's wife. Despite the problems, the two women end up bonding and forming an unlikely friendship. When Kate discovers that Mark is still seeing someone on the side, she initially believes that it is Carly but she and Carly eventually discover that Mark is seeing a third woman, a beautiful young woman named Amber (Kate Upton).
Carly and Kate travel to the beach, where Kate has a run in with Amber and the two women inform her that Mark has been cheating on all of them. They decide to take revenge by doing things such as spiking his smoothies with estrogen and giving him breasts, as well as putting hair removal cream in his shampoo. Through their pranks, they discover that Mark has been embezzling from various companies at his workplace and Carly begins to connect romantically with Kate's brother Phil (Taylor Kinney). In addition, Amber confides to Carly that she is seeing someone else as well. However, their camaraderie begins to shatter when Kate finds herself falling for Mark again after an investor's dinner and is upset when Carly exposes his fraud and offers to prove he didn't change and ask Mark if he wants to hang out.
Later, Mark goes to the Bahamas on a supposed business trip, Kate decides to follow him there and blow up his cover. She finds out Carly and Amber at the airport, who explain what Mark has been up to, using Kate as the owner of the companies Mark defrauded, which would cause Kate to go to prison if the fraud is discovered. She discovers that Mark has yet another woman and that he had been seeing her. This, and the possibility of facing prison in Mark's place, urges Kate to take actions with help from Carly's legal expertise.
When Mark returns from vacation, he goes to visit Carly at her office. He is then locked in the conference room by Carly's assistant Lydia (Nicki Minaj), and is shocked to find all three women together who then confront him with all of his infidelities and embezzlement they have discovered. With Carly as her attorney, Kate demands a divorce. Kate reveals that she has returned the embezzled money to the companies, which helps the divorcing couple avoid prison but leaves Mark bankrupt. On top of this, Mark's business partner Nick arrives and fires Mark upon the discovery of the crime and in addition offers Kate the chance to take over her former husband's job in appreciation of her honesty. Then as he begins to leave Mark breaks his nose running into a door, he ruined his suit falling on the walls of a glass room, his Aston Martin gets towed and, Frank hits Mark in the face in retaliation upon leaving. The film ends with Carly eventually marrying Phil and the couple expecting a child, Amber marrying Frank (which agonizes Carly upon finding out her father is Amber's romantic partner), and Kate working as a CEO with Mark's former business partners and the company making a profit under her leadership.