A new couple, Dan (Matt Walsh) and Meg Craverston (Maribeth Monroe), moves into Jeff's Cul-De-Sac. Meg mentions they bought the house sight unseen for cash. Karen informs Jeff about their new neighbors, Tim (Jon Hamm) and Natalie (Gal Gadot), inviting them over as a surprise upon Jeff's return home.
Jeff and Karen's relationship lacks intimacy, while Tim and Natalie are very affectionate. Karen discovers that Tim is a successful travel writer with hobbies like glassblowing, and Natalie is a trendy social media consultant and cooking blogger who helps Sri Lankan orphans. They are stunning, accomplished, and overly friendly with the Gaffneys. Tim presents Jeff with a glass figurine he claims to have made. Karen becomes curious when Tim casually mentions knowing Jeff works at MBI right after meeting him. Karen becomes suspicious of the Joneses after seeing Tim in Jeff's den at a block party and Natalie seemingly making a secret exchange at a cafe. Doubting Natalie's intentions, Karen follows her to the mall but gets caught in the dressing room. Natalie realizes Karen has been tailing her and confronts her.
Meanwhile, Tim invites Jeff to a Chinese restaurant, but Jeff believes that getting drunk and interacting with a snake head is not how to bond. He thinks true friendship involves shared experiences like indoor skydiving, which his friends do not enjoy. Throughout this, Tim attempts to get Jeff to talk about his coworkers. Tim and Natalia break into MBI HQ and find an email sent from Jeff's computer to an arms dealer named Scorpion. At home, Jeff accidentally breaks Tim's glass sculpture and uncovers a bug hidden inside. The couple realizes they've been spied on and decide to sneak into the Joneses' house to find the bug. Inside, they discover that the Joneses are targeting Jeff and the MBI staff. Jeff mistakenly stuns Karen with a pen gun, and they barely escape just as the Joneses arrive. Natalie worries Tim is getting too close to Jeff, but they admit their love, which is against the rules. Natalie sees the used pen gun and suspects the Gaffneys may have broken into their home.
The Gaffneys meet with MBI advisor Carl Pronger to discuss the Joneses, but he is killed by a sniper before revealing more information, and the Gaffneys are attacked. The Joneses rescue them, leading to a high-speed chase. They learn that the Joneses are investigating potential treason within MBI. Back in their neighborhood, Jeff offers relationship advice to Tim and Natalie, and the couples bond. After returning home, the Joneses activate a bomb that destroys their house. The Gaffneys discover the Joneses are secret agents. Later, while lying to the police about them, the Gaffneys prepare to flee when the Joneses unexpectedly appear in their basement. They have kidnapped Dan Craverston and his wife Meg, who were attempting to sell MBI's experimental microchips to an arms dealer known as "The Scorpion." The Scorpion (Patton Oswalt) aims to take out the Joneses and obtain the microchips that could compromise U.S. missile defense. Dan admits he contacted the arms dealer using Jeff’s computer. Jeff then accepts the Scorpion's offer over the phone, arranging a meeting with his wife at a hotel under the alias "Rascal Flatts" to deliver the microchips.
Jeff and Karen head to the hotel for the meeting, supported by the Joneses from the roof. The Scorpion is revealed to be Bruce Springstine, a former MBI employee who recognizes Jeff. As their cover is exposed, Tim calls for backup, but the operation is canceled, labeling the Gaffneys as collateral damage. The Joneses ignore orders and surrender to the Scorpion. While the Gaffneys and Joneses are held captive, Karen distracts their captors by kissing Natalie, allowing the Joneses to eliminate Bruce's men. They escape by leaping into a pool just before Natalie detonates a bomb that kills the Scorpion and his remaining henchmen. The Joneses, pleased with their new allies, bid farewell and return to their espionage activities. A summer later, Jeff and Karen visit Hazim's Cafe in Marrakesh, where they run into the Joneses, who reveal they've quit the agency. However, when they notice four men in fezzes, possibly from another agency, the Joneses engage in a gunfight with them, though the actual fight is not shown.