Before Peter Parker is revealed, Norman Osborn is seen in his lab, speaking to a man called 'Justin', about the Greek myth of Arachne. Osborn receives a phone call, he gives Justin a spider to hold while he takes the call. Osborn talks about Oz, a 'wonder drug'. Justin throws the spider into an empty container while Osborn finishes the talk, saying that the Oz testing has gone well on animals, especially on spiders, and that human testing will come soon. The spider then crawls out of the container it was thrown into; the next panel shows us the markings on the spider's back, two orange "O's", in contrast to its dark body.
On Earth-1610, Peter Parker is a lonely high-school student, who is constantly bullied and harassed by Flash Thompson and his sidekick, Kenny 'Kong' McFarlane. In fact, the two have a game where they throw things at Peter or kick him, and then give each other points. Peter seems to be interested in Mary Jane, and the two are friends, yet Peter seems to be too shy to ask her out or even talk to her during lunch. Harry Osborne is also a friend of Peter's, and he tries to defend Peter against the bullies, asking them to leave him alone. In the school gymnasium, Peter is, of course, less athletic than everybody else; his own gym coach calls him a 'woman'. At home, Peter is quiet, but still gets along well with his aunt and uncle, who are very fond of him, glad that he is smart and contemplative. Later, when Harry comes over to Peter's house to study, they go down into the basement, where Peter keeps his lab equipment, computer, and a chalkboard covered with equations that Peter's father wrote. Peter begins speaking about a molecular adhesive his father was developing, until Harry becomes bored and leaves. Harry goes home, where he tries to talk to his father, but is blown off. His father, a very busy, important man, has no time for Harry. The next day, Peter and his classmates are on a field trip in Oscorp Industries. Suddenly, while taking the tour, Peter is bitten on the hand by a massive, black spider with two "O's" on it's back. Peter screams in shock and shakes the spider off; it lands on Mary Jane, who hits it with her notebook; it lands on the floor, where Kong smashes it with his shoe, saying, 'Die!' Peter immediately falls down and throws up; Peter then faints. On the bus ride back to school, Mary Jane comforts Peter, telling him that it 'could'a happened to anyone.' When Norman Osborn finds out, he arranges to pay the hospital bill and send a fruit basket to Peter's family, because he wants to keep an eye on Peter. Aunt May and Uncle Ben decide not to sue, instead just to accept Norman's apologies and make sure Peter is alright. At school, Flash and Kong make fun of Peter more than ever, for throwing up and for fainting. The cheerleaders also make fun of Mary Jane for being friends with Peter. Kong tries to kick Peter in the behind, but Peter senses the kick coming, dodges it, grabs Kong's foot, and flips him in the air, smacking Kong down onto the floor. After doing this, Peter suddenly snaps his head back and faints. He awakens in a hospital, where a doctor asks him a few questions, and his blood his collected. The blood is stolen by somebody working for Norman Osborn; Norman has his scientists look at the blood, where he learns that the Oz formula in the spider's venom is killing Peter. Norman sends one of his men, 'Shaw', to kill Peter. Shaw attempts to run Peter over in his car, but Peter somehow, miraculously jumps to avoid the car, flipping in mid-air and landing perfectly on his feet. Shaw crashes into a tree; Peter runs up to help, but Shaw pulls a gun; Peter's spider-sense kicks in again and he flees the scene. Shaw then aborts the mission. Peter, amazed at his new-found abilities, blows the next day of school off, staying in his lab in the basement, where he researches spiders all day long. When Aunt May and Uncle Ben confront Peter about him skipping school, the conversation turns heated and Peter is sent to his room. Later, in the early morning, Peter tries climbing his wall, and finds himself able to hang upside-down on the ceiling with just his hands and feet, exclaiming, 'Whoa-- Cool.'
Peter is then shown in class; he seems shaky and nervous. Suddenly, he snaps his head back violently and shoves his hands forward, crushing his desk in his grip. The class, previously sleeping through the teacher's lecture, wakes up; Flash and Kong make fun of Peter for being a 'spazoid', while the teacher finds him another desk. Peter later goes to the bathroom, where he finds his muscles have grown and now are defined. Peter is later shown in gym class about to shoot a basketball; Flash attempts to hit on Mary Jane, but when he grabs her arm, Peter throws the basketball into Flash's face from across the gym, knocking Flash down. Peter tells Flash to leave her alone, and Flash tells Peter to meet him at three o'clock, presumably for a fight. Peter apologizes to Mary Jane, who thanks Peter for getting Flash off her back. Later, Flash and Peter are fighting in an alley, surrounded by their classmates. Peter dodges several of Flash's punches, telling him 'I'm serious, Flash, I don't want to fight you...', to which Flash punches again; this time Peter puts up his hand to block Flash's fist; Flash falls to the ground, yelling and nursing his hand. Peter is genuinely surprised and sorry that he hurt Flash; later Kong tells Harry that Peter broke Flash's hand. Norman overhears the conversation and tells Harry that he'd like to give Peter a personal tour of the labs; Harry agrees that Peter would enjoy that. Later, Peter finds out that Flash's parents want Aunt May and Uncle Ben to pay the $2500 hospital bill, otherwise they will sue. Aunt May and Uncle Ben decide to pay the bill, rather than pay a lawyer, even though they don't have the money. Aunt May and Uncle Ben try to talk to Peter about the incident; Peter yells, ' I' am so sick of being picked on all the time! For once I defend myself and what do I get from you? I get a lecture!' Peter then runs up to his room; May and Ben reassure themselves that the incident was just a result of Peter's growing pains. Later that night, Peter runs out of the house and goes to an old warehouse to test out his new abilities; he is able to jump from the floor of the warehouse over twenty feet straight up and land on his feet, on the ceiling. He is then able to land catlike on his feet, falling from the ceiling. Peter then picks up an old car in the warehouse, lifts it over his head, and throws it down. The next morning, Peter apologizes to May and Ben for yelling at them last night; he hugs Ben, then leaves to take the tour around Oscorp. While viewing the equipment, Doctor Octavius immediately starts talking to Peter about the accident with the spider, then asks Peter for a blood sample. Peter refuses, so Octavius sneaks up behind him, shoves a needle in his arm and takes the blood. In shock and repulsion, Peter sprints out of the lab. Harry chases him, but when he looks out the exit into the parking lot, he can't see where Peter ran to. When Norman looks at the blood, he realizes that Peter is no longer dying; in fact the situation has reversed, and Peter is healthy now. Norman reveals that his next plan is to inject himself with Oz; he tells his scientists to crunch some numbers and get the next phase rolling on.
Peter, Flash, Kong and MJ are at a wrestling event, where Crusher Hogan, a massive, muscular man built like an ox, is showing off to the crowd. The announcer offers $500 to any man who can defeat Hogan in the ring. Kong attempts to take the offer, but the announcer declines as he is too young. Flash tells Peter to go try it; Peter makes a joke about Flash suing Hogan's family in reference to Flash's parents suing Peter's aunt and uncle for Peter breaking his hand. MJ leaves, disgusted with the argument. Later, at home, Peter is shown trying on a mask, black with mesh covering his eyes and red surrounding the mesh. Soon, Peter, while wearing the mask, is back at the wrestling event and jumps in the ring. The announcer tries to get ID from him but Crusher is annoyed by Peter and decides to fight him. Kong remarks, 'Damn, man, I shoulda thought of that.' Before Hogan can punch him, Peter licks him up, over his head, and smashes him down into the ground, to the wide-eyed shock and awe of the audience. The announcer again attempts to find out who the masked man is; but Peter grabs his money and leaves, not before making a promise to show up again sometime soon. Later, Peter puts the $500 in an envelope and slips it under the door; he writes a note, making it seem as though the faculty at Midtown High donated the money, feeling the incident with Flash was 'unfair'. Later at school, the basketball coach asks Peter to play basketball on the team, since he was holding back and the team is short one player (Flash, because his hand is broken). Flash protests outright, making Peter angry, so Peter agrees to go to after-school practice to see if he can play on the team. Later, Peter is seen playing in a game; it is clear that he has dunked the ball several times, and Midtown High is leading 114-26. Later, MJ asks Peter to do a geometry project with her on Monday- Peter has to turn her down because he has another wrestling event on Monday. Peter is shown in the ring again with Crusher, easily overpowering him and throwing him down yet again. The announcer, feeling like Peter needs a stage name, yells out, 'The Amazing Spider-man! The Spectacular Spider-man!' Later, Peter receives his money from the manager of the club, who attempts to get Peter's name and number; Peter declines. The manager then gives Peter a costume, remarking that his current get-up is dorky. Peter slips the money under the door again, so that May and Ben don't find out what Peter is doing for the money. Peter tries on the costume upstairs; It looks exactly like the classic red and blue costume used in the 616 universe, only without a web pattern and a spider. Peter remarks that a large spider in the center of the costume and some webs should look good. Later, Harry walks into his father's lab, only to see Norman strapped up to a large machine of some type; Norman yells for Harry to leave. Harry does not leave, however, and sees his father scream, an ominous end to the volume.
The next volume opens on a scene of destruction at Oscorp labs; Harry and Doctor Octavius are seen lying in the wreckage, as is several other doctors and scientists. A news reporter is speaking in the background, revealing that there was an explosion, an accident of some type at Oscorp, and there is speculation as to whether Norman was in the accident or not. Peter is shown throwing down Crusher Hogan yet again in the ring; after wining, Peter goes to collect his money, but the manager claims thath the money is gone. He angrily blames Spiderman for stealing his money, and demands he takes off the mask before he calls the cops. Peter immediately starts running and escapes. Peter is walking in the streets, changed into his street clothes, mulling over the past few days in his mind, when suddenly he hears a man and a woman screaming for help, that somebody had stolen from them. The robber almost runs into Peter; Peter doesn't stop him, but lets him run past. The man and woman ask Peter why he didn't stop the man, trip him or kick him, and Peter responds, 'Yeah, well, I've got my own problems, big guy.' Peter goes home to see his aunt and uncle in a bad mood; Peter's grades have been dropping ever since he took up basketball. Ben and May suggest that basketball might not be a good idea; to which Peter retorts angrily. In the end Peter ends up running out of the house, leaving his aunt and uncle incredulous at how strangely he has been acting lately. Peter runs around, jumping up walls and running along rooftops, when he reaches Kong's house. Peter, surprised that he is asking this, asks if he can crash at Kong's house. Kong lets him in. The next night Peter is still at Kong's house, where apparently they are having a party. Liz Allan, apparently drunk, begins talking to Peter while Flash is angered that Kong let 'Puny Parker' sleep over. Liz begins to kiss Peter, who doesn't object. Suddenly MJ shows up; seeing Liz and Peter kiss, she runs out of the house, with Peter running right after her. Peter runs right out of the door into Uncle Ben, who drags him out of the house. It is here that Ben gives Peter the famous talk, that 'With great power, comes great responsibility...' Peter responds 'My father... If he knew so much... then where the hell is he?!' Peter then runs away into the night, crying. Ben only looks at his fleeting shadow, sadly, saying, 'Come on Peter, snap out of it. You can d o it...' After this, a large, looming, dark creature of some type is seen jumping around, whispering unintelligible words, Prrrrkrrr. Peter is then shown on a rooftop, thinking over what Ben said to him. He finally decides it is time to tell May and Ben what happened with him and his powers. When Peter reaches home, however, he is greeted by wailing sirens and police cars surround his home.
Harry Osborn snaps awake in his mansion to the sounds of his mother screaming. Harry rushes out of his room but is too late; a fire has started in the mansion and his mother lies dead among the flames. Harry looks up to see a massive, horned, humanoid creature, with fire constantly burning on its hand. The creature seems to throw a fireball at Harry then flees; Harry runs out onto the grounds to see the massive creature, with a cape, flying, or jumping, away from the house. Next, Aunt May is shown, taking an interview from a police officer about the incident that night. May says that a robber came in the back door; Ben though it was a squirrel, so he went to investigate. It turned out to be a man with a gun pointed at them, demanding they give him all their money. Ben jokingly said 'You probably have more money than we do.' This apparently made the man mad, so he shot Ben, and seeing what he had done, fled back out the way he had come in. Ben's bodybag is then rolled out the door, causing May to gasp. The police in the room get word of a robbery occurring two blocks from the murder scene, with the robber trapped in an old warehouse, possibly the same man who murdered Ben. Peter begins to tear up and sprints out of the door. As Peter jumps around the rooftops, he pulls on his wrestling costume. The robber/murderer is seen holed up in the warehouse, with several police cars surrounding the entrance. Peter suddenly shows up in his costume; Peter beats him down, throwing him around the room and disarming him. It takes one punch to knock out the man. Peter grips the man by the collar and suddenly recognizes the face to be that of the man who robbed the deli store, the man whom Peter could have stopped, had he wanted to. (This scene was clearly made to look similar to the scene in Amazing Fantasy #15, very similar poses in the panels, a very fitting tribute.) Peter has a flashback of the incident where he could have stopped the criminal and prevented Ben's death. Peter looks at the man's ID, then throws him out the window, hanging him by a rope. The man is arrested while Peter watches, hanging on to a nearby wall. Peter thinks of what his uncle told him that fateful night, 'Great things are going to happen to you in your life, Peter. Great things. And with that will come great responsibility. Do you understand?' Peter looks into his mask, and whispers, 'I do now.' Peter is then shown defending people, stopping robberies and muggings, all the while thinking back to what his Uncle Ben told him, and finally understanding the meaning of those words. Peter promises himself and Uncle Ben, 'I will never let you down again, Uncle Ben.'
This volume opens up with J. Jonah Jameson speaking with his writers and staff at the Daily Bugle. Jameson orders them all to come up with a front page story on Spiderman, rather than on the Osborn's house catching fire or on the Kingpin. Peter is then shown in his basement, celebrating because he finally discovered how his father's molecular adhesive worked; he creates a web shooter and says, 'Spiderman has... webs.' Peter tests the adhesive, learning that it can support his body weight and stick to his ceiling. Aunt May tells Peter to get some sleep; the next day in school peter is seen fast asleep, snoring in class. When his teacher wakes him up, Peter snaps forward and breaks his desk again. The teacher threatens to talk to his coach if he falls asleep again; Peter reveals that he quit the basketball team already, so there'd be no point in that. Kong and Flash angrily confront Peter about quitting the team after class; Peter tells them it just wasn't like him to play basketball. Kong makes a belittling remark about Uncle Ben dying; before Peter can retort in full, Harry suddenly shows up at the school. Peter and MJ greet him, worried and excited. Just as they are greeting each other, Peter's spider sense goes off and deafening explosions are heard from a distance. The fire sprinklers go off, and the student run out the exits. Peter jumpsout a window, changes into his costume and runs aroun to the main entrance to combat whatever is causing the explosions. Peter runs through the halls and is suddenly confronted by a massive, cloaked creature that throws several fireballs at Peter; Peter dodges them all, offering witty remarks to the creature. Peter tries to lure the creature out of the school; the thing knocks him through a brick wall, and jumps into the air, holding onto Peter, grumbling the words, 'Prrrrkkkrrr....'
The creature, jumping dozens of feet into the air, suddenly throws Parker at the ground, meaning to kill him. Peter tests out his new webs, making a trampoline-like structure to absorb his fall; it works, and Peter is safe. Peter uses his webs to swing back up and kick the creature in the back, and then repeatedly punches it in the face, until the monster grabs Peter and throws him away. Police helicopters converge on the scene; just as Peter tries to web down the creature, he misses and instead webs up the windshield of one of the helicopters. Peter accidentally hits the other helicopter as well, blinding the cops. Peter chases the monster down to a bridge, where the helicopters once again converge, this time shooting the beast. Several bullets to the chest do not deter the monster, and it attacks Peter again. Peter dodges and the monster falls off the bridge into the freezing waters below. the police in the heli's attempt to arrest Spiderman, even threatening to shoot; Peter starts running and the police open fire. Spiderman dodges every last bullet and escapes. Peter goes back to school and hides under a chalkboard, and is found by the police searching the area. As Peter, Kong, Flash, and MJ talk about the monster, Harry suddenly appears and claims the monster was his father. Later, some bubbles coming up from the river near where the creature fell indicate it could have survived the fall somehow.