Peter Parker and Spider-Man are both on top of the world at the start of the movie. Spider-Man is extremely popular and Peter Parker has got the girl, the photo’s and is even making it to Mary Jane’s new Broadway Starring show. However not everyone is okay with that. At the opening night of the show, Harry Osborn is shown in the balcony looking at MJ and down towards Peter. After the show, Peter spots Harry, but Harry wants nothing to do with him. Peter then goes backstage to see MJ, who is clearly extremely excited after her first night on Broadway. The two have a date in the park where they look at the stars while in the comfort of Peter’s webbing. As they watch, a meteorite crashes in the park and an extra-terrestrial symbiote oozes out of the rock. Before Peter and MJ leave the park, it attaches itself to the back of his bike.
Meanwhile it appears that Harry has taken the Goblin Serum as he looks towards his table of updated equipment. Also, in an unidentified apartment, a man, seemingly an escaped convict enters a bedroom of a young girl. It is revealed that this girl is his daughter and that he has escaped prison. His daughter is very sick and his wife wants nothing to do with him. His name is Flint Marko and he claims he was wrongfully accused of a crime he did not commit. He promises to get his wife the money they need for their daughter, but she yells for him to leave.
Peter then goes to visit Aunt May and tells her he wants to propose to MJ. She tells him a man must put his wife first. Peter believes he can and Aunt May gives him the ring that Uncle Ben proposed to her with. With the ring in his pocket, Peter rides through the city on his bike. He is then ripped off his bike by Harry on a flying glider that is more on par with a snowboard. The two fight along the rooftops and in the ensuing chaos, peter nearly loses the ring Aunt May gave him. While slinging through an alleyway, Peter sets a line that knocks Harry off his Glider, however, by doing so injures Harry to the point where he has temporary amnesia. Peter takes him to the hospital where he acts like the man he was before his father died.
The Police have caught up with Flint Marko and basically have him cornered in a facility. While running away, he falls into a sand pit that is actually a particle accelerator. With no escape Flint is caught in the research field, unbeknownst to anyone. He disintegrates into the sand. However, the next day, seemingly, a sand figure emerges. He learns how to control the power he has been given.
MJ’s play doesn’t get a favorable review, particularly MJ herself. She is hurt by the paper’s assessment of her talent. Peter, in an attempt to comfort her comes across as a little arrogant when he talks about overcoming criticism as Spider-Man. When he realizes this he tries to comfort her, but there is trouble and Spider-Man is needed. The black symbiote now is in Peter’s apartment.
An out of control crane crashes into a building that has a photo shoot going on. It is revealed that the photo shoot is of one of Peter’s classmates, Gwen Stacy. The crane crashes into the building, causing a partial collapse. Meanwhile on the ground Police Captain Stacy is introduced to Gwen’s supposed boyfriend, Eddie Brock, a rival photographer to Peter Parker. After Spider-Man saves Gwen from falling off the building, Brock tries to approach him stating that he is the new photographer in town. Spider-Man is not a fan of this. Later, when Peter arrives to sell the pictures to J. Jonah Jameson, Brock is there and has his pictures chosen over Peter’s. Brock and Peter are then told that there is a staff opening for photographer, Jameson tells them that whoever gets a picture of Spider-Man committing a crime will get the job.
Later at a ceremony honoring Spider-Man for saving Gwen, he re-enacts the kiss that MJ and him first shared with Gwen, while MJ looks on. In the middle of the ceremony it is reported that there is a bank robbery. Sandman robs a bank and Spider-Man is unsuccessful in apprehending him.
Later that night Peter prepares to propose to Mary Jane at this fancy French restaurant. His plans for proposing don’t go so well. Mary Jane is already a little frustrated as she had been fired from her show. When she arrives, Gwen Stacey stops by the table to thank Peter for helping her in class and introduces herself to MJ as Peter’s lab partner. Once she leaves Mary Jane wonders if he is pushing her away. She is furious that he shared their kiss with another woman. She leaves the restaurant in a fury and Peter fails to propose.
The next day Peter tries to call her, however she ignores his calls and his message. Police Captain Stacey then calls Peter and Aunt May into the Police Station. It is revealed that Peter’s Uncle was killed by another man. This man is revealed to be Flint Marko, the Sandman. Peter begins obsessing over finding Marko, sitting in his costume listening to the police radio. When Mary Jane comes to visit him, he does push her away. She tells him everyone needs help, even Spider-Man. As Peter falls asleep listening to the Radio, the Symbiote, crawls towards him and covers his costume. Peter wakes up hanging upside down on a skyscraper with no knowledge of how he got there or where this new suit came from.
Curious about the suit, Peter brings a sample to his friend and professor, Curt Conners. Dr. Conners warns him of its symbiotic behavior. He tells him not to get any on him. Once home, he hears of Marko robbing a bank over the police wire. Instead of opting for his traditional red and blues, he goes for the dark black suit in order to apprehend him. As he catches up to Sandman, the suit starts feeding and fueling his anger towards Sandman. His strength increases as well as his recklessness. When Brock tries to take a picture of Spider-Man in his new costume, he smashes his camera. Brock pulls out a digital camera and takes some pictures. Meanwhile Spider-Man has followed Sandman underground and seemingly dorwns him with a surplus of water.
The suit continues to feed on Peter, making him easily moody. When his land lord asks for his rent, he outbursts angrily and slams the door uncharacteristically. Peter becomes aware of his behavior and takes the suit off and goes to visit Aunt May to tell her that Spider-Man killed Marko. She warns Peter that revenge is like a poison.
Meanwhile Mary Jane is feeling lonely and instead of calling Peter she calls Harry. The two banter playfully in his house. While cooking an omelet the two share a moment that MJ immediately regrets and leaves abruptly. This causes Harry to regain his memories and his partial insanity. He sees his father and is told to attack Spider-Man’s heart. Mary Jane arrives home and hears a message on the answering machine from Peter. Before she is able to answer, Harry, in his goblin attire threatens to kill Peter if she doesn’t do as he tells her to do.
The next day Mary Jane and Peter meet at a park and she breaks up with him. When his pleas become too much she painfully cries there’s someone else. Peter, heartbroken, goes to a café to talk to Harry, where he reveals that he is the other man in her life. As Peter leaves he turns around and sees the devious look in Harry’s eyes. Furiously Peter returns home and gives himself over to the Black Suit. He then confront Harry at his house and the two fight. Peter, fueled by his fury and the suit, relentlessly attacks Harry, going as far as emotionally challenging him. Harry throws one of his pumpkin bombs towards Peter, but before it explodes Peter sends it back to Harry, disfiguring his face.
The following day Peter sees a picture of Spider-Man apparently stealing from the bank that Sandman actually did. The photo is Brock’s however Peter knows this didn’t happen. He goes to the Bugle and confronts Brock about this, when Brock pleads with him not to say anything about the forged pictures, Peter angrily responds to the staff that they should check their sources next time. It is revealed that the picture is photo shopped and Brock is immediately fired.
Peter walks around the city with an arrogance that is not lost on some of the people around him. At the Bugle he begins to flirt with Betty Brant. Dr. Conners tells Peter that if he has any of the symbiote left he should get rid of it because it feeds on aggression. Elsewhere the Sandman begins to reform from the attack that left him a pile of mud. Later that night, Peter learns that MJ is working at a jazz club and takes Gwen there in an attempt to make her jealous. Gwen soon realizes that this is all an act for her, and she apologizes to MJ and runs out, clearly upset. Peter then tries to talk to MJ, but the bouncers are preventing that from happening. His aggression fueled by the symbiote overcomes him and he attacks the bouncers. In an effort to stop Peter, MJ is struck by him. She is sent flying and asks him who he is, Peter doesn’t know.
Realizing the suit is taking complete control of his actions he goes to a church tower and tries tearing the costume off. It doesn’t seem to be working, however Peter struggles reveal the suits weakness to sound. At the same time, Eddie Brock is in the church and asks God to kill Peter Parker. Hearing the church bell ringing because of the struggle between Peter and the suit, Brock investigates and see’s Peter’s face as the suit slowly drips down. It reaches Brock and soon takes him as Peter is finally released of the symbiote, unaware that Brock has become one with the suit, Venom.
Later, at Peter’s apartment, Aunt May visits and Peter confides in her that he hurt MJ and doesn’t think it will be okay. She tells him he’ll find a way to make it up to her somehow. Meanwhile, Sandman is trying to find Spider-Man and runs into Venom. They make a deal because they both want the same thing, Spider-Man dead.
Venom kidnaps MJ by pretending to be a Taxi Driver. He suspends her cab at a construction complex. Peter see’s this on the news and finally breaks out the old Red and Blue Costume, becoming the hero everyone remembers. He knows that he can’t fight both Venom and Sandman on his own. He stops by Harry’s and pleads with him to help him. Harry refuses, angrily telling him to leave. Harry’s butler then tells Harry that his father died from his own Glider.
As the crowd watches in utter horror, a girl screams"LOOK" As everyone turns there heads, Spider-Man arrives at the construction site, greeted with roaring applause. As he reaches the cab mary jane screams"look out!" Venom then throws him through the car’s windshield. He reveals himself to peter as Eddie Brock. As the battle begins, Venom pins peter down saying that you destroyed my life and now I'll destroy yours. Peter tries to warn him against the dangers of the suit, but Brock refuses to listen, and becomes Venom once again. Just as he is about to make finishing blow, mary jane throw a brick at venom's head giving peter just enough time to break free and slip through the venom's webs causing them to fight in mid air. As the air battle insues, venom gets the upper hand and Peter falls to the bottom, where Sandman is waiting for him. Because of the massive amount of sand at the site, Sandman becomes a behemoth. As Spider-Man tries to escape is tied, by the throat, to a steel bar, by Venom as Sandman relentlessly pounds his fist on Spider-Man. When all hope seem lost, a bomb is thrown into Sandman’s face and it is revealed that Harry has come to help Spider-Man.
The two friends fight back to back, Spider-Man against Venom and Harry against Sandman. Harry is able to take down Sandman and sends Peter after MJ as he takes on Venom. Harry attempts to stab him, but Venom grabs the hoverboard and throws him down. Venom almost stabs Spider-Man with the board, but Harry jumps in front of him, being stabbed like his father was. Venom throws Harry down a few floors. While falling Harry hits some rebars which make a certain type of sound. Through this, however, Peter remembers the annoyance the Symbiote had to certain sounds. Peter circles Venom with the bars, and the clanging sound pains Venom as each one is slammed into the ground. Peter grabs Eddie from inside the suit with his webbing and pulls him out, once free he then throws a bomb from Harry's glider at the symbiote. Eddie rushes towards the symbiote while the bomb flies through the air, and is killed in the explosion.
Sandman approaches Peter and tells him that the killing of Uncle Ben was an accident. He got startled when his partner ran into him making his gun going off and hit Uncle Ben. Sandman tells Peter that his Uncle was trying to help him, even with a gun pointed at him. Sandman then goes to explain that the only reason that he committed the crimes was to save his dying daughter. Peter forgives him and Sandman looking at peter with thanks for the forgiveness he just received, drifted away in a sand cloud through. the buildings. Peter swings down to Harry where Mary Jane is trying to comfort him, Peter joins in. Mary Jane asks to go get help, but harry says that all he wants is to be with his best friends. And saying that dies with peace of mind and heart.
Peter, MJ, Gwen, Aunt May and several others attend Harry's funeral. Later MJ is singing at the jazz club. She stops singing as Peter walks in, and then he steps forwards, his hand reaching out to her. She takes it and the two embrace, slowly dancing.