The film starts with a trivia night competition at a bar. Two teams are competing, and the most competitive members from each team, Max (Jason Bateman) and Annie (Rachel McAdams), meet when they answer the same question correctly. The two start dating as they start beating their friends during their game nights until Max proposes to Annie during a game of Charades, and the two later get married and play each other at a dancing game.
In the present day, Max and Annie are trying to have kids, but when they visit Dr. Chin (Camille Chen), they learn that they are having trouble conceiving, which is attributed to Max feeling stressed out lately. Annie figures that Max is stressing over his older, more successful brother Brooks (Kyle Chandler) visiting that night, as he has always been upstaging Max throughout their lives.
Max and Annie return home to prepare for their game night later that evening. They run into their creepy neighbor Gary (Jesse Plemons), who used to attend game nights with his wife Debbie (Jessica Clair Lee) until their divorce. Everyone finds him really weird and annoying, so his only company is his dog Bastian. Gary notices they are setting up for a game night, but the couple denies it so they won't have to invite him.
The couple's friends arrive later that night. There's childhood sweethearts Kevin (Lamorne Morris) and Michelle (Kylie Bunbury), and dim-witted Ryan (Billy Magnussen), who brings a pretty but equally dim date, and the others point out that he always loses because he brings dumb girls with him. The friends sneak in by climbing in through the windows since Max and Annie told them to do so since they don't want Gary to know they really are having a game night. Unfortunately, this is ruined when Brooks pulls up in a Stingray (Max's dream car) and makes it painfully obvious to Gary that Max and Annie lied to him. When Brooks does join the game, he hijacks it by telling the party about an embarrassing story from Max's childhood when he supposedly tried to blow himself. This throws Max off his game and he and Annie lose. Brooks then invites everyone to go to his house the next week for game night. Annie becomes upset because she feels Brooks is deliberately screwing with Max and ruining their chances of conceiving. She supports Max in taking Brooks down the following week.
During the next game night, everyone shows up at Brooks's really nice house. Ryan brings a new woman, Sarah (Sharon Horgan), whom he brought because she is significantly smarter than all the other girls he's brought with him. Brooks starts the party off by having everyone do a drinking game of "Never Have I Ever". When the matter of sleeping with a celebrity is mentioned, Michelle takes a drink, which makes Kevin feel insecure as he didn't know about this in the whole time they were together.
Moments later, a man, "Agent Henderson" (Jeffrey Wright), enters the house with FBI dossiers that will serve as clues that will lead them to go on a hunt for kidnappers, and the winners get Brooks's Stingray, which gives Max more of an incentive to win. However, two real kidnappers break in, knock out Henderson, and start attacking Brooks. Brooks fights the two men all around the house while everyone thinks it's part of the game. Brooks is eventually taken, and the gang looks over the dossiers to read the clues. Max and Annie leave when they figure their clue out, while Sarah manages to get in touch with the people who made the game so that she and Ryan can get a step up, and Kevin and Michelle are trapped in Brooks's office when Ryan leaves them in there as they have found a clue. Kevin tries to climb through the ceiling over a stack of boxes, causing him to topple over and knock the door open.
Max and Annie are led to a bar, with Annie having taken a real gun that fell out of Brooks's pocket during the struggle, but she thinks it's a prop. In the bar, they see Brooks in the back room and hold the men in the bar at gunpoint while they try to get to Brooks. When they find him, Brooks says none of this is part of the game and that he is in real trouble with real bad guys. Annie then fools around with the gun until she fires it off and sees it's real. She accidentally shoots Max in the arm, causing him to bleed severely. The bad guys start to break in, so Max and Annie grab Brooks and run out. As they drive away, Brooks admits that his success never came from working on Wall Street like he's always claimed, but rather because he's been smuggling stuff, and he stole a Faberge egg from a criminal called The Bulgarian and sold it to someone named Marlon Freeman. The villains then find Max and Annie's car and go after them. Brooks jumps out of the car so that Max and Annie can get away, leading him to get taken again.
Ryan and Sarah go to the publishing company and meet Glenda (Chelsea Peretti), who just came from a murder mystery party where she was the corpse, so she startles the two. They have to bribe her into giving up the next clue. Meanwhile, the actual actors playing kidnappers show up at Brooks's house, leading Kevin and Michelle to realize that everything that happened earlier was real. They get in touch with Ryan and Sarah after learning the truth.
Max and Annie stop to buy supplies so that Annie can take care of Max's gunshot wound. It leads to her cutting into his bone, the two of them gagging uncontrollably, and then ultimately realizing that the bullet exited Max's arm earlier.
The group all go to Gary's house since he's a cop and would have a computer that has information on the aliases Brooks told Max. They are forced to play Jenga with Gary while Max goes to his office to use the computer. The office is full of memorabilia of Gary and Debbie when they were married. Max learns that Marlon Freeman is really a rich guy named Donald Anderton (Danny Huston), while The Bulgarian has evaded capture. Bastian then wanders into the room as Max's arm drips blood onto the carpet, and then onto the dog. Max tries to clean it off but only makes things worse. He then rounds everyone up to leave.
The kidnappers call Max and warn him that they'll kill Brooks within less than an hour if they don't deliver the egg. The group arrives at Anderton's home to find the egg. Anderton is holding a fight club in the basement, which Ryan and Sarah watch while the others go look for the egg. During their search, after much badgering over the matter, Michelle finally admits to Kevin that the celebrity she apparently slept with was Denzel Washington. She recounts the story and even has a picture, until Kevin has to tell her that it wasn't Denzel, but a guy who looks a lot like him. Meanwhile, Max and Annie bring up the matter of having a kid, which seems like less of something Max wants, which Annie deduces is because he wishes he were more like Brooks.
Ryan spots the egg in a vault and goes to grab it while everyone watches the fight. Unfortunately, he is spotted, and he runs away with the egg. Anderton's guards chase the group as they run around the house with the egg, but they finally manage to take it and leave the house.
The group arrives at the bridge where they must meet the kidnappers, but Kevin hits the brakes too hard, and the egg goes flying and shatters against the dashboard. They notice that something was inside the egg - a list of people in witness protection. The group approaches the kidnappers with the paper, and they force the group to get on the ground. While they speak to their employer, Brooks apologizes to Max for how he treated him and for lying to him. He tells Max the keys to the Stingray are in his jacket pocket. The kidnappers then decide to execute the group until Gary arrives and shoots them. Gary figured that something suspicious was up with the group with how they acted all night. One of the kidnappers then shoots Gary. Max and Annie go to help him until Max notices a blood capsule fall out of Gary's mouth. He reveals that he hired the kidnappers to take over Brooks's game night so that he can get back in the game. When the group hands him the WitSec list, Gary says he wasn't in on that. Then, The Bulgarian (Michael C. Hall) appears with his bodyguard and shoots Gary for real. Brooks swallows the list, so the villains take Brooks with him to their jet.
Max and Annie run to Brooks's house to take the Stingray and drive to the jet. As the jet is preparing to fly, Max manages to take out the wheels and cause the jet to go down. The Bulgarian's guard goes after the couple. Annie tries to distract the guard while Max goes to save Brooks. Max fights The Bulgarian while Annie is held at gunpoint by the guard. In the fight, the turbines go on, causing the guard to get sucked in and get shredded. Annie then knocks out The Bulgarian with a fire extinguisher, and the two of them free Brooks. He tries to play it off like this was also part of the game, but he's just kidding.
Three months later, the gang gathers at Brooks's house for game night since he is serving 3 years of house arrest. He says it's not all bad since he sold the WitSec list on the black market for $3 million and also tipped off the people on that list for $20,000 a pop. The group even has Gary rejoin them, but he still sucks at the games. They play Pictionary, and Annie uses it to announce to Max that she is pregnant. The two of them embrace while their friends congratulate them. We then pan outside to see two guys in masks with guns preparing to go into the house.
During the closing credits, we see a detailed look at how Gary planned to hijack Brooks's game night. After the credits, we see the man that Michelle mistook for Denzel meeting a new woman - Debbie.