NOTE: This spoiler was submitted by Jeremy

Moments after J Jonah Jameson (JK Simmons) outs Peter Parker (Tom Holland) as Spider-Man, Peter grabs MJ (Zendaya) to get away from the crowd of shocked New Yorkers who truly believe he orchestrated the London drone attacks from Mysterio. Peter swings with MJ to try and get away from crowds, but news choppers swarm them. They swing through the subways and manage to get away.

Peter and MJ make it back to the Parkers’ apartment, where Aunt May (Marisa Tomei) and Happy (Jon Favreau) have just broken up but soon see the news of Peter’s identity being exposed. While Peter tries to find out what happened with May and Happy, they see the news choppers outside the apartment, and Peter has no choice but to comply with authorities.

Peter, MJ, and Ned (Jacob Batalon) are interrogated by police for their perceived involvement in terrorist activities. MJ and Ned defend Peter, but he manages to find a lawyer to help drop charges – blind lawyer Matt Murdock (Charlie Cox).

Although Peter tries to return to a normal lifestyle, he is hounded by people who think he is either a hero or a menace. Peter tries to make it work per the assurance of his friends. They focus on their college applications, but they have all of them rejected because of recent events. Even their goal school, MIT, rejects them all. Peter feels responsible for his friends’ lives being ruined as a result of their association with him.

Peter visits the Sanctum Sanctorum to visit Doctor Strange (Benedict Cumberbatch) to ask him if it would be possible for him to turn back time to prevent people from learning his secret identity, but Strange thinks tampering with time was already risky when the Avengers saved the world from Thanos. He then comes up with an idea for a spell that could fix things, although Wong (Benedict Wong) warns Strange that the consequences could be catastrophic. After he leaves, Strange ignores Wong and takes Peter down to a lower level where he begins to cast the spell so that everyone will forget that he is Spider-Man. Peter starts to make changes in the middle of the spell, as he still wants MJ, Ned, May, and Happy to know that he is Spidey, and this causes the spell to destabilize and create a brief rift, but Strange manages to get it under control. When Peter mentions that he didn’t even contact the MIT administrator to talk to them about reconsidering for MJ and Ned before asking for the spell, Strange scolds Peter.

Peter gets in touch with Flash (Tony Revolori), who is claiming to be Spider-Man’s best friend and helps Peter try to reach the MIT administrator (Paula Newsome), as she is heading to the airport and is going across the Alexander Hamilton bridge. Peter makes it there through a traffic jam and begins to talk to the administrator, but his Spidey Senses go off. Mechanical tentacles begin bursting from beneath the bridge, and people begin fleeing their cars. Rising from under the bridge is Dr. Otto Octavius/Doctor Octopus (Alfred Molina). He addresses Peter, who suits up as Spidey to fight him. He tries to rescue the administrator, but Doc Ock keeps attacking him. When the admin’s car goes over the side of the bridge, Spidey manages to web it up safely before Doc Ock catches him under the bridge and rips off a piece off the Spidey suit’s nanotech, which attaches itself to his tentacles. However, thanks to the suit’s programming, Peter is able to control the tentacles and uses them to pull the admin up to safety. Otto then observes that this Peter is not the Peter Parker he is familiar with and whom he blames for his failed reactor experiment. She tells Peter that he is a hero and that she will talk to the board about MJ and Ned’s applications, as well as his. Just then, a cackling figure throws a pumpkin bomb onto the bridge and blows up some cars. Norman Osborn/Green Goblin (Willem Dafoe) rides in, and Otto recognizes him, but Peter is then pulled through one of Strange’s portals.

Strange shows Peter that he has created holding cells in the Sanctum, where he keeps Otto, as well as Dr. Curt Connors/The Lizard (Rhys Ifans). Strange says that because of Peter tampering with the spell, people from other multiverses that know Peter is Spider-Man have broken through. Strange gives Peter a magic gauntlet that allows him to capture the multiverse figures, and Peter brings in MJ and Ned to help out. Strange allows them to help from the Sanctum’s basement. While they try to locate the others, Otto notes that it’s impossible for him to see Norman since he died years earlier before Otto became Doc Ock.

Peter goes out at night towards a field with huge electrical towers. He witnesses Max Dillon/Electro (Jamie Foxx) siphoning energy from the towers, and when he calls out to Max, he begins to fire electrical bolts toward Spidey. He is protected by Flint Marko/Sandman (Thomas Haden Church), who remembers how Peter Parker helped him after an earlier adventure, but Peter has to explain that he is not the Peter that Flint knows. Peter then rips off the charges from the tower to bring Max down. His formerly glowing blue body returns to his normal appearance. Peter then uses the gauntlet to send Max and Flint to the holding cells.

Norman snaps out of his Goblin persona and smashes his helmet before retreating to the FEAST center where May works. She calls Peter and tells him that he is there. Norman appears unstable, rambling about how he is in a place he is unfamiliar with, and mentions his son (Harry). May encourages Peter to help Norman.

Jameson continues reporting against Spider-Man on his show, and he gets word from his guys about Peter’s location to try and catch him for a big story.

Peter brings Norman to the Sanctum, where he recognizes Otto. Flint notes that both Norman and Otto are dead in his universe, while Lizard recognizes Max from his formerly nerdy appearance, and Max acknowledges the Lizard’s rampage across New York where he tried to turn everyone into creatures like himself. Strange then comes in with a relic called the Maquina de Cadavas, which contains the botched spell and will be used to send the villains back to their universes. However, after Peter learns that they are all fated to die fighting Spider-Man, he feels that there is an alternate way to fix things. He swipes the relic from Strange and flees into the streets with it. Strange separates Peter’s spirit from his body, but his reflexes help him dodge Strange, and he gets himself back together to continue fleeing. Strange then pulls Spidey into the Mirror Dimension as Peter still tries to convince Strange there has to be a better way to fix things without letting the villains die. When Spidey realizes that the Mirror Dimension is like geometry, he is able to find a way to trap Strange in web and secure the relic before escaping and leaving Strange there and taking his portal creator.

Peter proposes an alternate plan where he will cure the villains of their corruptions before sending them home to avoid their fates. He leaves the relic with MJ and Ned (as well as the portal maker) before taking the villains to his and May’s new apartment where he finds the components necessary to get the job done. Peter shows the villains a Stark fabricator that will make what they need, but Max is drawn to the energy given off by the arc reactor.

With Norman’s help, Peter develops a new chip for Otto that will allow him to be in control of the tentacles rather than the other way around. Otto returns the nanotech to Peter’s suit, and Peter gives Max a device that will drain the electric power from his body. Unfortunately, his Spidey Senses go off, and he catches Norman reverting to Goblin in an attempt to sabotage the plan. Goblin convinces Max to embrace his power and reject the cure. Max and Flint retreat together while Lizard breaks out of the truck he was in. Goblin tosses Otto out the window, but he escapes just as Jameson and his crew. Spidey fights Goblin as the villain smashes him through the floors of the building while May grabs the Goblin antidote and runs. When they catch Goblin at the floor level, May attempts to inject him with the antidote, but it doesn’t work, and Goblin uses his glider to strike May before making his escape and firing pumpkin bombs at the news crew and officers outside. May picks herself up and goes to Peter. He blames himself for this and feels that he should have listened to Strange, but May tells him he did the right thing and reminds him that “with great power comes great responsibility.” They start to leave, but May realizes she has been gravely injured. Peter stays by her side as she dies. The SWAT team comes to surround the building and fire at Peter, but he escapes. Happy drives by and sees May dead, and he is apprehended by authorities.

May’s death is reported on the news, with Jameson blaming Spider-Man, and Peter feeling immense guilt over it. MJ and Ned try to use the portal maker to locate Peter. Ned manages to get it to work and finds Peter…except it’s not THEIR Peter. This other Spider-Man (Andrew Garfield) jumps out through the portal into Ned’s grandma’s room. He convinces MJ and Ned that he is Peter Parker. When Ned tries again, he finds yet another Peter Parker (Tobey Maguire). The two Spider-Men meet, and Tobey-Peter says that he has been trying to locate the Peter of this universe to try and help him. Since MJ and Ned don’t know where to find him, the two Peters figure he must be somewhere that they usually go to get away from their problems. MJ knows where to find him.

MJ and Ned find their Peter on the roof of the building where they hung out at earlier. They console him over May’s death, and he expresses his remorse over trying to help the villains. The other Peters come out to try and talk to Tom-Peter, but he doesn’t want to hear it, as he is now consumed by rage and hatred for Goblin. Tobey-Peter brings up how he wanted the man who killed his Uncle Ben to die, but when he got his wish, it didn’t make him feel better. Andrew-Peter mentions his guilt in failing to save Gwen Stacey. When Tom-Peter eventually realizes what his variants have gone through, he knows that he cannot let May have died in vain.

The three Peters (plus MJ and Ned) continue to work to create the cures, while also bonding and being amazed by each other’s unique abilities (like Tobey-Peter’s organic web shooters). Tom-Peter expresses his worries to MJ, who assures him that she will be by his side. He then makes a call to the Daily Bugle for Jameson’s show to talk to all of New York and assure them that while he created this mess, he will fix it.

The Spider-Men lure the villains to the Statue of Liberty where they are adding a Captain America shield, while MJ and Ned guard the relic. The Peters talk about other past experiences, like Tobey-Peter fighting the symbiote and Tom-Peter fighting Thanos, while Andrew-Peter laments fighting Rhino, but the other two assure him that he is still “amazing”. Soon, Sandman, Lizard, and Electro make their appearances and begin to fight the Spider-Men. While the heroes try to administer the cures, they keep getting knocked down. They resolve to take specific targets, and the three Spideys swing together in action. Tobey-Peter fights Sandman but manages to give him the cure so that he can return to being Flint, and Tobey-Peter promises to bring him home to his daughter. Lizard chases MJ and Ned when he sees the open portal, causing them to run out onto the scaffolding. Tom-Peter manages to get Lizard and turns him back into Curt. Electro proves to be strong, but Otto reappears and helps Andrew-Peter by removing the arc reactor with his tentacles and placing the cure onto his chest. While Max is remorseful, Andrew-Peter doesn’t hold anything against him, and Max is thankful.

Goblin comes flying in on his glider for the attack. Ned manages to get Strange out of the Mirror Dimension and he watches the three Spideys in action. Goblin causes the scaffolding to break down, and MJ falls over the edge. Tom-Peter tries to rescue her, but the glider hits him. Andrew-Peter jumps in and saves MJ, and he briefly appears to feel redeemed for Gwen. Tom-Peter uses one of Goblin’s bombs to break down the glider and crash onto the collapsed Cap shield. He webs Goblin down and begins to pummel him in fury. Tom-Peter then grabs the glider and prepares to impale him, but Tobey-Peter comes in and stops him. Goblin stabs Tobey-Peter in the back, and he begins laughing at Tom-Peter for failing to save May, but he injects him with the cure and completely removes Goblin from Norman’s body, and he feels great remorse for hurting his Peter.

A rift then opens up in the sky, with more potential villains about to break through the multiversal barriers, and Strange says he can’t stop them from breaking through. Peter then suggests a final spell where not only would people forget that he is Spider-Man, but they will forget about him, period. This means that even Strange, MJ, Ned, and Happy will all forget who Peter is, but it is the only way to fix things. Peter bids his variants farewell with a group hug, all acknowledging each other as brothers, and he goes to tell MJ and Ned what has to happen. Ned tearfully bids his best friend farewell, while Peter and MJ profess their love for one another and share one last kiss before he leaves. Everyone is then returned to their own universe.

Jameson continues to slander Spidey in the media. Peter now lives alone, with nobody knowing who he is. He goes to the cafe where MJ works and finds her and Ned. They are still friends and have both gotten into MIT. Peter talks to MJ for a moment before walking away. He later visits May’s grave, where Happy is as well and asks how Peter knew her. He says “through Spider-Man”, and both he and Happy acknowledge how many people May helped.

Peter returns to his apartment, where he uses a police scanner to listen in on any criminal activities. He then continues to fulfill his duties to protect New York as Spider-Man.

Mid-Credits Scene: Eddie Brock and Venom (Tom Hardy) are at a bar after they were also pulled through from their universe. After Eddie learns from the bartender about all the Avengers activity, he and Venom are immediately sent back to their universe after the spell is cast. However, a small piece of the symbiote remains in this universe.

Post-Credits Scene: A trailer for “Doctor Strange in the Multiverse of Madness” is shown, showing Strange dealing with the repercussions of the multiversal rift and having to team up with Wong, Wanda/Scarlet Witch (Elizabeth Olsen) and America Chavez (Xochitl Gomez) to fix things while also battling Baron Mordo (Chiwetel Ejiofor), as well as a dark variant of Strange known as Strange Supreme.

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After Mysterio exposes Peter Parker as being Spider-Man, New York City is divided on whether they view him as a hero or a menace. Although Peter tries to continue living a normal life, MJ and Ned are also affected with their college applications due to their association with Peter. He goes to Doctor Strange to try and cast a spell for people to forget that he is Spider-Man, but Peter's tampering with the spell causes a break in the multiverse that sends people from other universes that know Peter Parker is Spider-Man into this one. This includes past Spidey enemies - Norman Osborn/Green Goblin, Otto Octavius/Doctor Octopus, Max Dillon/Electro, Flint Marko/Sandman, and Curt Connors/The Lizard.

When Peter learns that the villains are fated to die fighting Spider-Man in their worlds, he tries to stop Strange from sending them back and traps Strange in the Mirror Dimension. Peter tries to come up with cures for the villains to be rid of their corruptions so they can go home and not suffer tragic ends. While it works for Doc Ock, the Goblin persona takes over Norman and stops himself from getting cured, also convincing Max and Flint to not go through with it. Aunt May is killed trying to help Peter fight Goblin, and Peter blames himself for her death.

MJ and Ned uses Strange's portal creator to summon the other two Peter Parkers from the villains' homeworlds to help their Peter get back on his feet and find a solution. Together, they create the cures and face off the villains on the Statue of Liberty. Otto comes to help as well, and Max, Flint, and Curt all turn back to normal. Goblin fights Peter and is nearly killed by him, but the Peter from Goblin's universe stops him, and they help cure Norman. As an even bigger multiversal rift happens, Peter tells Strange to cast a spell that will make everyone in every universe forget that Peter Parker is Spider-Man, which will mean that it will be like Peter never existed. He says goodbye to MJ and Ned, as they will not have any memory of him, and everyone is sent back to their own universe.

Peter continues to keep an eye on his loved ones while continuing his duties as Spider-Man. Meanwhile, Eddie Brock and Venom (who were sent there after "Venom: Let There Be Carnage") are pulled back to their own universe after the spell works, but a small piece of the symbiote remains.