The movie opens with a close-up on fingers furiously typing on a keyboard. Files are being deleted from a system. Spiders kept in tubes as research test subjects are killed en masse with poison gas. A bespectacled figure checks vials, some of which feature the skull and crossbones. A shot reveals it's Peter Parker's father, Richard Parker (Campbell Scott). Suddenly, his computer access is cut off and he can't complete his mission to destroy the project files. Richard dashes from the Oscorp building on his way home to Peter and his wife, Mary (Embeth Davidtz) .
Richard is recording a message with a webcam. "People will say I'm a monster for what I've done". He hears Peter call for him and cuts his message short. Rushing up from the basement, he sees that the house has been ransacked. Someone is looking for the files he took. A car pulls up as Mary says goodbye to Peter. Richard grabs her away. Peter is clearly distraught. He touches Richard's hand for one last time and stares at them from the front door.
Richard and Mary are on a private jet. Mary mentions that she has found somewhere safe for them to stay as Richard uploads project files from his laptop. He tries to reassure her, explaining that their life has been changed forever. Richard doesn't want to put Peter through that. Mary pops into the bathroom just as one of the flight crew steps out of the cockpit. Richard notes the man has gone to a sink and appears to be washing blood off his hands. He is VERY suspicious and wary of the guy's behavior. Suddenly, the crew guy pulls a gun and threatens Richard. He locks Mary in the bathroom and prepares to shoot Richard. As Richard uploads the file, Mary realizes something is wrongs and bursts out. A struggle ensues and Mary is shot! Richard desperately overcomes the thug. Mary reminds Richard to finish the upload just as the thug roars back to life!
They scrap back and forth as we see the pilot (Timothy Adams) is dead and the plane falls into a steep dive. Thug shuts down the laptop again as Richard realizes his fate is sealed. Mary is dead; there's no getting out of the situation. However, the file upload to Roosevelt has to be completed. Richard shoots out a window and holds onto the laptop with the strongest Cat-5 cable in existence. The hitman flies out the window to his death and Richard confirms that the file is transferred. The plane plummets to its doom and cut to black.
Music rings in as the camera follows Spider-Man falling to earth. A stunning sequence follows Spider-Man playing webbing his way through the city. He overhears a helicopter radio announcing a plutonium shipment under siege at Oscorp. Spidey swings into action to help. A big tow truck is being driven by a bald guy with a Russian accent, Aleksei Sytsevich (Paul Giamatti). He's bashing lots of Manhattan vehicles as he tows/steals the Oscorp truck. Armed assistants set explosives to blow the hatch as the Russian rolls over police cars. Spidey swings impressively through buildings in hot pursuit.
The goons (Dusan Hyska & Andrei Runtso) blow the hatch and hop into the van. There's a container of yellowish vials that are their target. Spidey hops onto the tow truck and engages in some Spidey banter with Sytsevich (who clearly has no idea who he is). As the goons prepare to hijack the plutonium, we cut to a Oscorp employee the socially inept geek Max Dillion (Jamie Foxx) stumbling through a crowd with an armful of blueprints. Naturally, the prints get knocked from his hands and roll into the street JUST as Spidey and Sytsevich barrel around the corner. Spidey leaps to the rescue and prevents Max from being squashed by a cab. Spidey hands him the plans and notes that he works at Oscorp before leaping away.
Sytsevich, clearly ignorant of the dangers of radioactive material, slams into a bunch of cars, tossing the goons and the P-238 around in the van. Dozens of cop cars crash into the truck pinning it in. The goons burst from the van firing at the cops with automatic weapons. Strands of web shoot from above, yanking the goons and suspending them over the cops. Sytsevich takes his chance to escape. The P-238 is bouncing all over the place as Spidey tries to avert disaster, catching, juggling and swinging like a chandelier. As he bounds out to recover one last vial, his phone rings. Gwen Stacy (Emma Stone) is at their high school graduation waiting for him. He's really late. As he playfully banters with Gwen he imagines that he sees her disapproving father riding by in an NYPD patrol car. He remembers his broken promise to leave Gwen alone (from the first Amazing Spider Man film).
Gwen is called up to deliver her valedictory speech. Peter isn't there. Cut back to the truck chase. The next sequence bounces back and forth between the speech and Spidey trying to stop the truck. Parker's Spider sense triggers into a slow motion shot as he leaps over a bus to protect some pedestrians. FINALLY, Spidey subdues Sytsevich, grabs the P-238, makes it to graduation and kisses Gwen on stage! (Note: Spider Man and comic book creator Stan Lee has a cameo as an elderly man at the graduation who sees Peter change out of his Spider Man costume).
Aunt May (Sally Field) takes pictures of the new graduate before sending him off with Gwen. They make a date where Peter will join Gwen and her family for Dim Sum at 8:00 pm. Peter catches a glimpse of Captain Stacey standing with his family and hears his voice in his head. That evening, Peter shows up to the date, but won't come into the Chinese restaurant that Gwen and her family are at. Gwen meets him at the door and they talk again about her dad and the promise Peter made. Peter is torn, but Gwen really isn't having it. Peter loves her, but he couldn't handle losing her because of his actions. Gwen decides to break it off. She's done.
The next morning, Peter is on another visually stunning city patrol. Falling and swinging as the wind ripples his Spidey suit. As a radio call-in show plays in the background, Spidey rescues a grade school kid and his science project. He encourages the kid, much like he did with Max at the beginning of the movie. During an extended montage, a talk radio debates rages while he saves a girl, changes clothes, saves a bodega and mingles with costumed New Yorkers. Of course, he still keeps an eye on Gwen every now and then.
After a cute scene with Aunt May, we cut to Max Dillon, who has really flipped out after his chance meeting with Spider-Man. He seems to have created an alternate Spidey persona with whom he engages in a meticulously crafted fantasy. Oscorp is developing a new power grid system and Max is part of the team. Max's delusion may have spilled over into his work life too. He shares an elevator with Gwen with whom he shares his Spider-Man story. Unbeknownst to him, Gwen appreciates his fascination.
Meanwhile, Harry Osborn arrives home to visit his ailing father. Norman looks awful; his skin is discolored and his hands are claw like. He's bedridden and looks like he's at the end of his rope. Norman derides Harry for not achieving more. They have a fractured relationship. It is as bitter as Norman's illness. He says the disease is genetic and implies that Harry will succumb to the same fate. He asks to see Harry's hand and notices that it is shaking; a symptom of the illness. He hands Harry a drive with his research. Minutes later, a newscast announces Norman Osborn's death.
Gwen receives a quick message about good news regarding her scholarship; meanwhile, most of Oscorp is being allowed to leave early to attend a memorial for Norman, but Max is told by his supervisor (B.J. Novak) to stay behind and check out a problem with the bio-electric power grid. The room is a mess of electric eel tanks and strange equipment. Max calls a colleague to deactivate the system for safety purposes, but the colleague refuses, saying he's on his way out the door. Max nevertheless tries to repair the system, but ends up electrocuting himself and falling into the tank of eels. His transformation has begun.
Meanwhile in a boardroom, Harry is being informed of various Oscorp troubles. He twirls the drive while responding to the information. He couldn't care less about it all, and sees that the Board doesn't respect him. Consequently, he lashes out with his disdain for them, elevating his father's assistant, Felicia Hardy (Felicity Jones), as his second-in-command. Charm doesn't run in the family. Peter Parker is announced, raising eyebrows in the room. Harry steps out to see Peter. They haven't seen each other in years. He came to check in on his old friend in the wake of his father's passing. After an awkward moment, the friends reconnect with a laugh.
In a local riverside park, Harry and Peter catch up. Harry seems genuinely happy to get away from his Oscorp drama and they bum around the city together. Harry apologizes for the distance in their relationship which leads to a conversation about why Peter's parents left. Harry also learns that Peter has a girlfriend, and Peter says Gwen's name, mentioning she's an Oscorp employee. A van is monitoring their conversation which turns into a discussion of Max's accident. He's to be written off to avoid another scandal.
Cut to the lab where Dillon's corpse has been stashed. In the midst of electrical interference, Dillon's body reanimates in a shower of sparks. Electrical tools jump to life as Dillion discovers the nature of his powers. Grabbing a coat, Dillion/Electro Man stumbles out of the lab.
That evening, Peter meets with Gwen in the city. Looks like they're making up. They have real chemistry and they both seem a lot happier in each other's presence.
Meanwhile, Dillon steps into the street and immediately sets off all the car alarms. He sucks the electricity right out of a car. As he looks up, he sees the city as a matrix of electrical energy. Max Dillon wants more and heads to Times Square.
Back to Pete and Gwen. He admits that he's been watching over her. She knows he's still in love with her. It's a nice moment. "It's the closest I can get to being with you." Suddenly, Gwen drops a bomb. That phone call was about a scholarship to Oxford. She's one of two finalists and could be headed to England. As Peter tries to process the news, his spider sense triggers. He looks to Times Square.
Max grabs a power outlet to draw in the energy. He doesn't appear to have any motivation other than to absorb the energy. A cop demands that he stop and Max inadvertently flips a big truck with his electromagnetic powers. As a fleet of cop cars surround him, he catches a glimpse of himself on the big TV monitors. It's the attention and stardom he's craved his whole life. His emotions explode triggering a wave of energy that flips the squad cars. Spidey swoops in to catch one before it crushes a cop and tries to talk Max down.
At first Max seeing his hero seems to improve his mental state. Spidey tries to talk him down a bit, begging the police snipers to lay off. Unfortunately, they take a shot, setting him off. As the crowd rallies behind the Spider Man, Max's inner dialog goes into overdrive. Convinced that he has been betrayed, he grabs some electrical cables, jacking them into his chest and sucking huge amounts of electricity into his body. Times Square goes dark and Max/Electro sends a blast of power that tears the block to shreds. Electro sends lightning bolts into the screaming crowd, levitating on electromagnetic force. Spidey sprays a fire hose onto him, disrupting Electro's power and sending him plummeting to earth. Electro is down for the count and Spidey heads home to watch the news about the fight.
Glancing at his busted web shooter, Peter becomes consumed with solving the mystery of his parents' disappearance. He feverishly starts research on the internet trying to connect the dots.
Meanwhile, Harry is sitting in a cavernous office. He's listening to news coverage fiddling with the drive his father left him. He feels an itch on his neck and as he reaches to scratch it, the drive pricks his finger. Falling to the desk, the drive causes a reaction with the desktop display and begins spitting out information about a secret battle armor. Harry looks at more files, and sees a video of Richard Parker explaining research into mutated spiders
Cut to Peter experimenting with ways to Electro-proof his electronic web shooters by watching YouTube videos. The next morning, his phone rings. It's Harry asking to see him. Harry says he's dying and needs Peter's help to save his life. At Harry's office, a video of Richard and Norman is playing. They are talking about how spiders might be merged with human DNA to achieve miraculous cures. Harry is convinced that Spider-Man is the key to success. Harry needs to find Spider-Man and experiment on his blood to find a cure.
Meanwhile, Gwen starts looking through Oscorp files to find Max Dillon. She thinks that he might be the electrical creature that attacked the city. Security agents detect the file access and block it, and then trace it back to Gwen.
Cut back to Harry, who thinks Peter has a relationship with Spider-Man. He needs Peter to put them in contact. The scene cuts back and forth between Harry/Peter and security people tracking Gwen's inquiries. They start to chase her and she bumps into Peter. Hopping into a storeroom, she explains that she knows who Electro is. Peter explains that Harry wants Spider-Man's blood and is fearful of the consequences. But back to business, Peter doesn't want Gwen to go to England. They kiss and attempt to exit the building. Gwen hops into an elevator with Harry Osborn. Harry figures out that this is the Gwen who has a relationship with Peter.
Cut to an exterior shot of Ravencroft Institution where Dillon has been collected and stored. Clearly, this isn't a benevolent place. Dr. Kafka explains that he wants to help Dillon. Max is incredulous as he recognizes Oscorp tech. After a few attempts to assess the limits of his powers, Dillon christens himself Electro. Scheming Oscorp exec Donald Menken (Colm Feore) commands that he be shut down and Electro is placed back into the neutralizing water chamber.
Back at Peter's house, Aunt May is sitting in the midst of Peter's conspiracy web about his parents. He confronts her about the truth and demands answers. She explains that he was dropped off on their steps with no explanation. She begins to ramble in frustration and will not reveal anything more about his parents. Peter explains that he doesn't want to replace her, he just needs to know the truth. May relents and tells him that some government officials came to see them. They claimed that Peter's parents were traitors. It doesn't make sense to either of them. May says that Richard had a very normal routine of taking the D train to work every morning at 7 am, and came home at 6 pm.
Cut to Harry's house. He looks awful. Spider-Man has dropped in to explain that giving him his blood isn't possible. It could have deadly side effects. Harry doesn't care. He wants the blood, no matter the cost. Harry is clearly going over the edge. He is desperate and Peter realizes he's made a mistake. He's about to make another one by interrupting Gwen as she heads into her scholarship interview. Despite breaking his heart, he wishes her luck in the interview.
Peter takes his frustration out on his conspiracy web, tearing it apart. In the midst of the take down, he throws an electronic device that Richard owned, and it breaks open, revealing a large number of subway tokens stashed inside. He remembers what May said about Richard taking the D train. Entering Roosevelt and the D train together on the internet, he learns about a secret subway station along the D line that was used to transport President Roosevelt, the same person Richard was trying to send the data to in the opening scene.
Back at Oscorp. Harry is in a drunken fit. He's sure that his fate is sealed since the super spiders were destroyed. Felicia, however, thinks there's still a chance. Apparently, Oscorp extracted the venom as a failsafe before killing the spiders. Harry begins combing through files to find the cache of venom. Apparently, Menken has been using Harry's security clearance to run the off-books Special Projects division at Ravencroft. Harry watches the Electro footage as Menken bursts into his office. It's a setup! Menken uses the Electro fiasco to remove Harry from his job and wrest control of Oscorp.
Peter is in the subway tunnels looking for his dad's lab. He discovers the Roosevelt station and activates a switch with a token. Gradually, the tracks open to reveal a subterranean lab car that roars to life. All of his dad's research is here and the file download was completed years ago. Richard's video explains Norman Osborn's nefarious deeds while proclaiming his own innocence. Richard Parker refused to let his research be used for biological weapons.
At Ravencroft, Harry breaks in to meet with Electro, stunning two guards and taking their access badges. Back to Peter, Richard announces that he used his own DNA with the spiders, meaning that only someone with HIS bloodline can replicate the experiments. That's why only Peter could inherit the Spider-Man powers without harm
Harry races through the Ravencroft facility activating a fire alarm.
Peter watches as his father says that Peter is the most important thing to him, driving Peter to tears.
Harry strips off his disguise and enters the chamber where Electro is being held. He cancels Electro's sedation. Harry bargains with Electro to take down Oscorp for him. Harry appeals to Max's desperate need for friendship and they agree to take down Spider-Man together Of course, Electro exacts revenge on Kafka before escaping with Harry.
Meanwhile, Peter leaves the subway station and receives a voice mail from Gwen. She's been accepted to Oxford and is already headed to the airport to avoid a face to face goodbye.
At Oscorp, Electro kill Menken's security guard before Harry walks in and forces Menken to grant him access to Special Projects. Electro dashes off to reclaim his stolen power grid design and cripple the city. In Special Projects, Harry injects himself with the spider venom "cure", which sets off a painful transformation into the Green Goblin as Menken escapes. Harry is in extreme pain and looks up to see the special armor from the hard drive video. Crawling painfully while green light flashes all around him, he makes his way to the suit. Upon entering it, a healing protocol begins to repair the damage to his ravaged system.
Cut to Gwen, caught in bridge traffic on the way to the airport. Her taxi driver (Teddy Coluca) sees that Spider-Man has webbed a love note on the bridge that draws Gwen out of her cab. He scoops her up and carries her off to talk. He's in love with her and they have the "movie love talk" on top of the bridge. Peter will go to England to be with her. As they kiss, Electro takes down the city's power grid, enveloping New York in darkness (and severely complicating air traffic). Gwen says there's a reset switch at the plant, but if Electro fries that, the city will never get back up. Brainy Gwen also figures out that Peter can Electro-proof his web shooters by magnetizing them. They do this with jumper cables from a squad car and Peter webs Gwen to a car for safety.
Electro is a living field of electricity that dwarfs whole city blocks. He challenges Spider-Man to settle their score setting off a dazzling sequence of Spidey jumping around Electo-blast and grabbing his webbing like a maniac.
Meanwhile, the flight Gwen missed is getting pretty desperate for contact with ground control. Their own instruments are being affected by Electro's field. What's more, ANOTHER flight is on an intercept path.
Spidey tries to short circuit Electro, but he's grown too powerful They trade punches and Electro literally spits electricity onto Spidey's head. Gwen's magnetizing trick works allowing Peter to toss Electro into the power grid and gain a moment's breather. Unfortunately, Electro is back in seconds and starts pummeling Peter as he bounces between the grid towers. Spidey is taking a pretty bad beating until Gwen runs over Electro with a Squad car. Gwen insists on staying and they work out a plan to defeat Electro. Spidey will distract him while Gwen resets the system. It's a big impressive fight sequence with Spidey using his spider sense to evade electrocution.
Spider-Man creates a web to channel Electro's energy and cues Gwen to flip the switch. The backlash restores the city's power and seemingly destroys Electro. The restored power avoids the plane collision and all seems well. Until Harry comes screaming in on his goblin glider, cackling maniacally. Seeing Spider-Man and Gwen together, Harry/Green Goblin figures out that Peter is Spider-Man and decides to hurt Peter by harming Gwen. Peter pleads with him to let Gwen go. Harry/Green Goblin obliges, by dropping her from his glider. Peter jumps to save her, but Harry drops a pumpkin bomb to finish the job. A furiously fast fight ensues, with Harry and Peter duking it out while Gwen attempts to avoid becoming collateral damage.
Gwen falls and Peter webs her stopping her descent. Harry pounces and pins Peter to a clock wheel. As the mechanism moves, it will cut his web and send Gwen to her fate. Peter pins Harry and wedges his foot on the mechanism to spare Gwen, but to no avail. The wheel turns, the web snaps and Gwen falls. The clock damage takes out Harry and Peter leaps through the wreckage to save his love. The web line catches, but the impact snaps her neck, killing her instantly. The pose mimics the comic book perfectly. Peter gently cradles her lifeless body, pleading for her to stay with him.
Cut to her funeral. Mrs. Stacy (Kari Coleman) is devastated. Peter and Aunt May hang back until the family leaves. Peter sits alone at her grave and a series of shots show him watching over her site over a period of several months.
At Ravencroft, Harry is in a cell. A visitor shrouded in shadow (the same man from the end of the first film) visits and discusses a plan. Spider-Man is grief-stricken and out of action. Harry has a plan and wants to "keep it small." Apparently, all that they need is at Oscorp. They decide on using Aleksei Sytsevich as a test subject.
Cut to a shot of Oscorp tower. Mr. Gustav Fiers (Michael Massee), who is the shadowy man walks through a room with specialized gear; Octo-arms (for Dr. Octopus), vulture wings (for Vulture), and an armored Rhino suit.... They will spring Sytsevich and set him against the city.
At the Parker house, a newscast indicates that Spider Man has been missing for five months. Aunt May expresses concern that Spider-Man has disappeared. Peter is consumed with remorse, but in his bedroom he grabs a USB stick and watches Gwen's graduation day speech. The speech is all about maintaining a sense of hope. Remembering her bravery, he opens his closet and takes the uniform.
Aleksei Sytsevich, controlling the mechanized suit as The Rhino, has just robbed a bank and is rampaging through the city. His superior armor is cutting through the cops. Inspired by his hero, the science fair kid has donned a Spidey suit and runs out to face the Rhino. Laughing at the sight, Rhino takes the bait and marches toward him. Until the real Spider-Man swoops in. Rhino charges Spidey who swings a manhole cover against Rhino....
Fade to black. End credits.