The film stars Andrew Garfield in the title role as Spider-Man/Peter Parker, with Emma Stone as Gwen Stacy and Rhys Ifans as Dr. Curt Connors. The Amazing Spider-Man delivers thrills despite having some similar elements to the 2002 Spider-Man film because they were following some of the same source materials of the comics.
A young Peter Parker discovers his father Richard's study has been broken into. Gathering up hidden documents, Peter's parents take him to the home of his Aunt May and Uncle Ben, then mysteriously depart. Years later, a teenaged Peter attends Midtown Science High School, where he is bullied by Flash Thompson and has caught the eye of Gwen Stacy. At home, Peter finds Richard's papers and learns his father worked with fellow scientist Dr. Curt Connors at OsCorp. Faking his way into OsCorp as one of a group of high-school interns, Peter sneaks into a lab where a "biocable" is being created from genetically modified spiders, one of which bites him. On the subway ride home, he is shocked to find strange spider-like abilities manifesting.
After studying Richard's papers, Peter visits the one-armed Connors, reveals he is Richard Parker's son, and gives Connors his father's "decay rate algorithm", the missing piece in Connors' experiments on regenerating limbs based on lizard DNA. Connors is being pressured by his superior, Dr. Ratha, to devise a cure for the dying, unseen head of OsCorp, Norman Osborn.
In school, attempting revenge on Flash, Peter gets in trouble, forcing Uncle Ben to change work shifts in order to meet with the principal; he tells Peter to pick up May tonight for him. Peter later goes to OsCorp and helps Connors regenerate a limb on a laboratory mouse, while ignoring a call from Ben. When Peter returns home, Ben scolds him for having neglected to pick up May. Peter storms off and Ben goes searching for him. Peter visits a convenience store, where a thief steals from the till and dashes out. Peter refuses to give chase. The thief runs into Ben, who confronts him. They wrestle over a gun, and Ben is shot. The killer escapes as Peter finds his uncle, who dies in his arms.
Afterward, Peter uses his new abilities to hunt criminals matching the killer's description. After a fall lands him inside an abandoned gym, a luchador-wrestling poster inspires him to create a mask to hide his identity. He also adds a Spandex suit, and builds mechanical devices to attach on his wrists to shoot a biocable "web".
Peter accepts a dinner invitation from Gwen, and he meets her father, police captain George Stacy. After dinner, Peter and Gwen go to her apartment building's roof, where he shows her his abilities and they kiss.
Ratha says Connors must begin human trials immediately if Osborn is to survive. Connors refuses to rush the drug-testing procedure and put innocent people at risk. Ratha fires Connors and says he will test Connors' serum at a Veterans Administration hospital under the guise of flu shots. Connors tries the formula on himself. After passing out and awakening, he finds his missing arm has regenerated. Learning Ratha is on his way to the VA hospital, Connors, whose skin is growing scaly and green, goes to intercept him. By the time he gets to the traffic-jammed Williamsburg Bridge, Connors has become a hybrid of lizard and man, tossing cars, including Ratha's, over the side of the bridge. Peter, now calling himself Spider-Man, saves each fallen car with his web-lines.
Spider-Man suspects Connors is the Lizard, and unsuccessfully confronts the creature in the sewers. The Lizard learns Spider-Man's real identity and attacks Peter at school. The police hunt both Spider-Man and the Lizard, with Captain Stacy also learning Spider-Man's real identity. The Lizard plans to make all humans lizard-like by releasing a chemical cloud from OsCorp's tower. Spider-Man eventually disperses an antidote cloud instead, restoring Connors and earlier victims to normal, but not before the Lizard fatally claws Stacy. The dying Stacy makes Peter promise to keep Gwen safe by staying away from her. Peter initially does so, but later suggests he may see her after all.
In a scene during the end credits, Connors, in a prison cell, appears to speak with a man in the shadows who asks if Connors told Peter the truth about his father. Connors replies, "No" and demands Peter be left alone before the man mysteriously disappears.
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