The film starts with Carly Whitten (Cameron Diaz) and Mark King (Nikolaj Coster-Waldau) engaging in a one night stand. Eight weeks later, they are in a relationship, and Carly is quite happy. She tells her friend and secretary Lydia (Nicki Minaj) about the relationship, where Lydia notes that Carly hasn't been with a single man in forever. Little does she know that Mark is married to a chatty woman named Kate (Leslie Mann).
Mark makes up an excuse to leave town for a few days, telling Carly there's an issue with the plumbing in his house. Carly is upset at this short notice, and she gets into an argument with Mark. He drops her off to have drinks with her dad Frank (Don Johnson), who is seeing a younger woman. He convinces Carly to show up at Mark's place to surprise him. She does so, dressing as a sexy plumber. She walks to his door and is greeted by Kate, who introduces herself as Mark's wife. A stunned Carly stumbles off the steps of the porch and trips backwards, knocking into a giant urn that she breaks.
An angry Carly storms into her office and tears up the flowers that Mark left for her. She tells Lydia that he is married, but Lydia suggests this could provide some kind of spice in their lives. Carly is later visited by a distraught Kate, who has a nervous breakdown upon realizing that Carly had slept with Mark multiple times. Despite all of this, Kate continues to find Carly and attempt to bond with her. Eventually, the two become unlikely friends. Kate later takes out her rage by destroying Mark's office with a golf club.
Mark comes home and takes Kate out, leading her to feel tempted into sleeping with him. As she's in the bathroom getting herself ready, Mark gets a phone call from another woman. Kate overhears and fakes feeling unwell to not get into sex. While she and her brother Phil (Taylor Kinney) are fixing up the walls, she breaks down and tells him that Carly is probably still having an affair with Mark. She later confronts Carly, who says nothing is happening and she's hurt by the accusation. They figure out that Mark is seeing another woman.
The ladies follow Mark to Miami and stay in Phil's beach house as they spy on Mark and his new lady. They find the couple at the beach, and both ladies are shocked to see the new, younger, and ridiculously hot girl named Amber (Kate Upton). Carly runs after Amber as she jogs down the beach, and Kate stops her. Amber sees them fighting in the sand, forcing them to tell Amber that she is getting played by Mark. Even though the ladies are mad at the same guy, they continue to bond and drink and laugh while Carly starts making a connection with Phil.
Kate says she wants Mark to really hurt, so all three ladies conspire to get the ultimate payback on Mark, utilizing Carly's job as a lawyer, Kate's knowledge of Mark's lifestyle, and Amber's looks to get revenge. Back in New York, Kate starts to mess with Mark by putting hair removal cream in his shampoo and give him loads of estrogen in his smoothies, causing him to grow breasts. Carly meets with Mark on a date, catches him flirting with another woman, and slips laxatives into both his scotch and water. He then shits his pants and has explosive diarrhea, then gets robbed when trying to get people to get him pants.
The ladies consider having one of them take one for the team and sleep with Mark to get more information out of him. They play Rock Paper Scissors, leading Amber to decide she'll do it. Things get more complicated when Mark takes Kate out for a romantic dinner with his business partner Nick (David Thornton). She starts to feel romantically connected to Mark, regardless of his adultery. Carly and Amber show Kate the next day a list of companies that Mark has invested in and embezzled money from. Kate doesn't feel as drive for revenge as before. Carly exacerbates things by texting Mark to hang out. The ladies walk out on each other.
Mark takes Kate to the Bahamas as he plans a business trip. Carly and Amber show up for Kate after Kate had given Carly an envelope with contracts from Mark's businesses, citing Kate as the CEO of the defrauded companies. They follow Mark from a hotel, where he is with yet another woman, whom he takes with him to the bank where he keeps his offshore money.
On the day that the ladies plan to make their move, Kate throws her engagement and wedding rings into the ocean. Carly and Amber sit by her side on the beach. They later take her to the bank to resolve the situation.
The final showdown comes when Mark is invited to Carly's law firm for a meeting. Lydia guides him to the conference room where Mark is forced to stand face-to-face with all three ladies. Kate immediately says she wants a divorce, but Mark refuses, trying to reel her back in with innocent apologizing. The ladies show Mark that Kate has returned all the money to the defrauded companies, leaving Mark with absolutely nothing while Kate gets the other half of his money. Nick comes in after being told the truth, and he fires Mark. Mark breaks down and loses his shit, throwing the papers everywhere and walking face-first into the glass wall, causing him to bleed. He runs to a computer and sees his bank accounts closed. He walks into a whole glass wall and he ruins his suit. He goes outside the building and sees his car getting towed. He screams in fury, and asks how this can get worse. Frank then comes out and punches Mark in the face, knocking him on his ass.
The ladies meet one last time and toast to their friendship. The ending text states that Kate works with Nick now and is the CEO of multiple successful companies. Carly and Phil became a couple and are expecting a kid. Amber started a relationship with Frank and they travel the globe to keep up with the summer season, though Carly refuses to call her "Mom."
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