On the night of his wedding to Elastigirl, Mr. Incredible takes enough time to stop crime in the city of Metroville. While he is attempting to capture villain Bomb Voyage during a bank robbery, Buddy Pine, a fan of Mr. Incredible, attempts to help acting as Mr. Incredible's sidekick "IncrediBoy". Buddy's interference almost kills him, and Mr. Incredible is forced to save Buddy and let Voyage escape, and barely makes it to the ceremony on time. However, as a result of Mr. Incredible's actions, the public begins to disfavor anyone with superpowers, fearing them and using litigation to stop them from harming the public despite trying to save their lives.
Supers are forced to abandon their heroic roles and adapt to regular life. Mr. Incredible and Elastigirl settle down in suburbia as Bob and Helen Parr and raise a family; their children appear to have super powers as well - the hot-headed Dash possesses super speed, while timid Violet has the ability to turn invisible aoutlining an offer for Mr. Incredible to stop a rogue robot, the Omnidroid 9000, on a distant island for a large sum of money. Bob accepts the job, and though the fight is difficult at first due to being out of shape, he is successful and reinvigorated. On the promise of more work from Mirage, Bob keeps up the pretense of still having his insurance job while he spends the days working himself back up into shape. Bob visits superhero suit designer Edna Mode (Brad Bird), who fashions a new supersuit for Bob, but refuses to add a cape as his request, noting that capes have caused the demise of many other heroes.
Bob soon receives Mirage's next offer and returns to the island where he is attacked by a new Omnidroid that lacks the weaknesses of the previous model. Bob realizes he has been misled: the Omnidroid is not 'rogue' at all: it actually takes direction from Buddy Pine, who is now calling himself Syndrome, and is attempting to get his revenge on Bob for having snubbed him as a sidekick years ago. Bob is forced to flee from Syndrome and the robot. Whilst in hiding, Bob discovers the skeleton of a former Super that gives him a clue about Syndrome's plans. Bob sneaks back into the island facilities and cracks Syndrome's supercomputer, from which he discovers that numerous Supers have lost their lives to the Omnidroids, with each engagement ultimately contributing to the development of less vulnerable Omnidroids.
Meanwhile, Helen has become suspicious of Bob's activities and discovers that he has visited Edna. She finds that Edna, in creating Bob's new suit, has created new suits for each member of the Parr family, including a homing device in each suit. Helen uses this to discover Bob's location on the remote island, but its signal alerts Syndrome and Bob is captured again. Helen procures a jet to find Bob, but finds Dash and Violet have stowed away. When Syndrome sends missiles to shoot the jet down as it nears the island, the three are able to escape using Helen's fireproof suit.
Bob tries to grab Syndrome but Mirage puts herself in the way. He threatens to kill Mirage if Syndrome does not let him go. Syndrome doesn't believe him and tells him to do it but Bob, unable to deny his moral code, is unable to kill her. On land, Helen frees her husband from the base while Dash and Violet avoid capture by Syndrome's forces. The four reunite but are re-captured by Syndrome, who reveals that he plans to launch the final Omnidroid to Metroville, using a remote control to act as if he was saving the city in order to gain superhero status. After the robot is launched, Mirage turns on her boss and helps the Parrs to escape and follow on a second rocket.
The Parrs arrive in Metroville to find the Omnidroid rampaging through the city, having used its ability to learn and cope with opponents to separate Syndrome from his remote control. Assisted by Frozone, the Parrs seize the remote control and take advantage of its design to destroy the Omnidroid. They then return home, where Syndrome, having discovered the Parrs' identity, is attempting to kidnap Jack-Jack and make him his sidekick. As Syndrome flies to his waiting jet, Jack-Jack's innate superhuman power manifests itself as the ability to shape-shift into a number of difficult-to-handle forms, the last being a devilish being, causing Syndrome to drop him. Bob throws Helen into the air to safely catch Jack-Jack, then throws his new car at Syndrome's jet, which causes Syndrome's cape to get caught in one of his jet engines, dragging him to his apparent death. The Parrs resume their normal life, albeit more contentedly with their status quo than before. But when the city is threatened by a new villain called the Underminer, the family of supers prepare to fight together ane.