The film opens in Lithuania where Drew Thayer (Justin Theroux) is on a spy mission. He is compromised and found by his targets, who chase him through the streets. Drew manages to kill the gunmen before making it to the home of his main hit and blowing that man up.
Meanwhile, in Los Angeles, Audrey Stockman (Mila Kunis) is given a surprise 30th birthday party by her co-workers, hosted by her best friend Morgan Freeman (Kate McKinnon) (yes that's her last name). One of Audrey's more obnoxious coworkers, Tess (Lolly Adefope), comes over and asks Audrey about her boyfriend, Drew, condescendingly telling her that Audrey doesn't seem like the type to go for someone like her, and Audrey is too embarrassed to tell Tess that her boyfriend broke up with her.
Audrey later gets a phone call from Drew after he's been ignoring her texts, but he doesn't answer when she picks up. Morgan takes Audrey's phone and messages Drew that they are going to burn his stuff, which they do.
We see a flashback to a year earlier when Audrey first met Drew in that very same bar. They appeared to hit it off just nicely. Then we jump back to the present where Audrey is working at a grocery store. A handsome man, Sebastian Henshaw (Sam Heughan), approaches her at the register. He gets her to walk with him to his car, only to reveal that he is an agent, and he orders Audrey into the van with his partner, Duffer (Hasan Minhaj). They inform Audrey that Drew is a CIA agent, which she was totally not aware of. They tell Audrey to report to them if Drew contacts her, and she mentions the phone call, but also that she didn't speak to Drew.
Audrey runs home to Morgan, who had slept with a creep she met at the bar named Viktor (Dustin Demri-Burns). She tries to tell Morgan about what just happened, only for Drew to suddenly make an appearance in Audrey's room. She asks if he really is a spy. Drew tries to explain himself, but she sees a sniper dot on his head. Someone starts shooting at Audrey's room, forcing her, Drew, and Morgan to take cover. Drew gives Audrey a second place trophy of his that she planned to burn, stating that it contains something very important that is wanted by an organization called Highland, and that they must meet in Vienna so she can deliver it to someone with the code-name Verne. Viktor them steps out and reveals himself as an assassin before he shoots and kills Drew. Morgan shoves him out the window to his death. Audrey and Morgan flee the apartment.
The two fly to Vienna after taking a whole stash of souvenir trophies in some luggage, and Morgan also smashes their phones for good measure. Once they arrive in Vienna, the ladies are picked up by a driver named Lukas (Kev Adams). Villains on motorcycles chase after them, and Lukas gets shot dead. Aubrey has to take the wheel and outrun the shooters, causing at least one to crash, and then having to throw off another one who's on the roof of the car. After he gets thrown off, he gets hit by a truck, and Audrey and Morgan ditch the car.
Audrey and Morgan arrive at the restaurant to look for Verne. Audrey finds Sebastian acting as Verne to take the package that Drew gave her. He tries to explain that everyone in that restaurant would kill her for it. Morgan then sees their waitress is named Verne, and she tries to tell Audrey. Instead, she blurts it out loud, leading all the other patrons in the restaurant to pull out their guns. Sebastian shoots at them, although he gets some help from Aubrey when she takes a dead assassin's gun and uses it to shoot another villain. With everyone dead, Audrey and Morgan run like hell out of the area. In order to avoid being detected at the border, they steal passports from two Australian tourists.
Sebastian meets up with Duffer as they contact their boss Wendy (Gillian Anderson). Sebastian realizes he got the wrong package, and Wendy reprimands him for his screw-up.
On the ride to their next destination, Morgan mentions the first night they met Drew and how he told her she was too much for her over-the-top demeanor. She says it hurt her feelings but she didn't want to tell Audrey because she saw how much she liked Drew. They then drop the trophy and break it open to find that Drew was hiding a flash drive inside.
Morgan gets in touch with her parents, and her father sets her up with a friend named Roger (Fred Melamed). He makes dinner for the ladies, but Aubrey starts to get sick. As she goes to puke, she finds the body of another man in the shower, the real Roger. Fake Roger brings out an assassin, Nadedja (Ivanna Sahkno). They order the ladies to give up the flash drive, and they hide in the bathroom as they try to find a safe place for it. Morgan tries to swallow it but cannot until Nadedja shows up and they are both knocked out.
Audrey and Morgan wake up to find themselves tied up. They encounter Drew's parents, Tom (James Fleet) and Marsha (Carolyn Pickles), who turn out to be Russian spies posing as his parents. They threaten to torture the ladies before Nadedja shows up to get information out of them. Audrey says that she flushed the flash drive down the toilet. Outside, Sebastian and Duffer are sitting in a van as Duffer attempts to order their fellow agents to start blowing up the spot. Nadedja goes to her tools until Audrey and Morgan start buying themselves time by spilling secrets about each other. Moments later, Sebastian shows up after knocking out Duffer and helps the ladies escape. Nadedja goes after them as Duffer orders the strike. Morgan kicks a grenade toward Nadedja and hits her, but only burns her face.
Sebastian drives Audrey and Morgan away. Audrey reveals that she kept the flash drive in her vagina because she knew it was too important to get rid of. He brings them to their headquarters to meet with Wendy.
Morgan contacts an old friend - Edward Snowden - and gets themselves set up somewhere safe. While there, Sebastian tells Audrey that she met Drew while he was on a job, and he says that what Drew felt with her had to be genuine because he clearly felt something too. Audrey thinks she is unremarkable, but Sebastian reminds her that she knew how to use a gun at the restaurant, she withheld information even under the threat of torture, and she has managed to get this far in the mission. Soon, the group are found by Duffer, who wants to sell the flash drive to whichever mafia group will pay the most. Before he kills them, a backpacker that the three are sharing a room with enters and thinks Duffer is a robber, so he slams Duffer to the ground, killing him.
The three take Duffer's body to dump, but Audrey takes his thumb off to use his phone to keep in touch with Highland. They want Duffer to make a drop with the flash drive at an event that night.
Audrey and Morgan go in disguise while Sebastian attempts to catch the villains. They end up at some kind of show where Morgan finds herself performing a trapeze act, but unfortunately, it's with Nadedja. As she tries to kill Morgan, Audrey ends up running into a very much alive Drew. As he tries to explain himself to Audrey, he goes through her bag looking for the flash drive, alerting her to his true motives. Meanwhile, Morgan is nearly strangled by Nadedja on the trapeze, but she uses what skills she learned way back when to lift herself and cause Nadedja to fall and get impaled on a spike.
Sebastian finds Audrey and Drew, just as Drew's fake parents come in to demand the flash drive. Drew fails to convince Audrey he's not bad, so he kills his fake parents and shoots at Sebastian. Drew tries to get the flash drive, but Audrey takes his gun from him and threatens to shoot him, only to reveal she took the magazine out. Police arrive, and Drew is arrested. Sebastian turns out to be okay because he was wearing a bulletproof vest. He and Audrey kiss. Morgan then contacts Wendy to tell her that the flash drive is secured, and she tells Morgan to let Sebastian know that he may report to work on Monday.
Audrey and Morgan then head out to enjoy the rest of their stay in Vienna.
Shortly after the end credits start, we cut to a year later where Audrey is celebrating another birthday. This turns out to be a cover as she and Morgan are now working with Sebastian to take down some villains.