By day, Peter Parker is an average high school student, gifted in his studies and ridiculed for his nerdy awkwardness by his peers. Once school lets out, however, Peter transforms into the "Spider-Man", the wise-cracking web-slinger protector of Queens, New York.
Ever since he accompanied Tony Stark on a "field trip" to Berlin, Peter has spent his days anxiously awaiting another chance to assist the Avengers. In the meantime, he's continued to operate around the city as Spider-Man, doing everything from stopping petty criminals to helping lost people(some with more success than others), occasionally reporting to a less-than-enthusiastic Happy Hogan. Unfortunately, Peter's desire to be ready for a call that he believes can come at any time has caused to him forsake much of his free time, to the point that he's begun quitting his extracurricular activities at school. His only remaining companion being his friend Ned Leeds.
One evening, Spider-Man arrives at the scene of an ATM robbery by crooks wearing Avengers masks. He is taken by surprise by the high-tech weapons the robbers wield, one of which malfunctions and nearly destroys a nearby bodega. Spider-Man saves the people in the bodega, but the robbers get away. To make matters worse, when Peter returns to his apartment, he finds Ned inside, having seen him take off his mask. Peter convinces an astonished Ned to keep his identity a secret from his Aunt May and everyone at school, but Ned blurts out during PE that Peter knew Spider-Man through his work at Stark Industries. Liz Allen, a girl who Peter crushes on and a Spider-Man fan, invites Peter and Ned to a house party she is hosting, and asks Peter to invite Spider-Man.
When Peter arrives at the party, however, he notices explosions in the distance and goes as Spider-Man to investigate. He sees a pair of criminals carrying out an arms deal with a petty crook using the same kinds of high-tech weapons as from the ATM robbery. He stops the arms dealers from killing their customer and chases them through the suburbs, only to be snatched into the air by their leader, a man in a flying suit of armor, and dropped into a lake. He is saved from drowning by Iron Man, being remotely-controlled by Tony while conducting business abroad. Peter describes the criminals and weapons he saw, and Tony warns Peter not to pursue these criminals any further.
Peter, however, is determined to get to the bottom of this case and bring in the arms-dealing gang to prove his worth.
Meanwhile, the criminals return to their lair. Their leader, Adrian Toomes, was a salvage worker who led the clean-up effort after the Battle for New York until his contract was rescinded and his job was taken by Tony Stark and the newly-formed Department of Damage Control. Embittered, he stole some of the alien salvage for himself and used it to make weapons which he then sold to criminals in order to support his family. He is extremely cross with one of his underlings from the failed arms deal for jeopardizing their operation and cuts him out of the operation. When the crook threatens to spill the beans on Adrian's criminal enterprise, Adrian silences him with an energy rifle that disintegrates him.
Peter manages to recover a damaged weapon from the arms dealers, and he and Ned study it and its immensely strong power source. When a tracking bug that Peter placed on one of the dealers indicates their base of operations is in Maryland, Peter rejoins his decathlon team, since they would be heading to Washington DC, only a short distance away from Maryland. Once in DC, Peter and Ned study the suit once more and find that, in addition to having a tracking beacon on it, it has a slew of hidden functionality locked behind a "training wheels" protocol. They disable the protocol and the beacon, so Peter can pursue the dealers without being monitored by Tony.
After turning down a chance to go swimming before the decathlon, Peter dons his unlocked suit, now accompanied by an AI he nicknames "Karen", and gives chase after the dealers. However, his unfamiliarity with the suit's many unlocked features puts him at a disadvantage against the dealers' leader, which causes him to be trapped in a DODC vault.
After taking some time to learn his suit's new functions, Peter learns from Karen that the power sources for the gang's weapons are actually unstable Chitauri explosives. He tries to warn Ned about the device after escaping from the vault, but it goes off when Ned accompanies the decathlon team on a trip inside the Washington Monument. Spider-Man manages to save his classmates from a collapsing elevator afterwards.
Back in Queens, Spider-Man tracks down the criminal from the arms deal he interrupted, who reveals that there is to be another arms deal going down on the Staten Island Ferry. Peter goes to stop the deal, but Toomes makes his escape as a malfunctioning weapon splits the Ferry in half. Peter struggles to keep the Ferry from sinking, and is aided by Iron Man.
Afterwards, however, Tony chastises Peter for overstepping his boundaries. Peter thought Tony didn't trust him, but Tony had actually believed Peter and was attempting to stop the arms dealers before Peter threw a wrench into his plan and needlessly endangered innocent lives, as well as his own. He orders Peter to give him back the suit he gave him in Berlin. When Peter argues that he's nothing without the suit, Tony scolds him: "If you're nothing without this suit, then you shouldn't have it."
With his "internship" now gone, Peter returns to a normal civilian life. He musters the courage to ask Liz out to Homecoming, and things seem to be going swimmingly for him as he makes his way to Liz's home to accompany her to the dance.
Unfortunately, he discovers that Liz's father is none other than Adrian Toomes, the leader of the arms dealers whom he recognizes from the Ferry.
On the drive to the dance, Liz mentions how Peter had been absent during the decathlon and the trip to the Washington Monument, leading Adrian to realize that Peter was the costumed vigilante that had been sabotaging his business. Once they are alone after Liz goes to greet her friends, Adrian warns Peter that if he tries to intervene again, he'd kill him and those closest to him.
Unable to let Adrian get away with his crimes and realizing he plans to rob a plane transporting Avengers' cargo, Peter apologizes to Liz and leaves, taking his old costume and pursuing Adrian to an abandoned building. Adrian uses his glider to bring down the building, trapping Peter so he can prepare to rob the plane. Peter, remembering when Tony told him "If you're nothing without this suit, then you shouldn't have it", musters the strength to escape from the rubble and pursue Adrian, thwarting his robbery and bringing the plane down on the coast of Coney Island. Adrian brutalizes Peter before trying to escape with some of the cargo, but his glider malfunctions and explodes. Peter rescues Adrian from his malfunctioning equipment and leaves him tied up for the authorities to apprehend.
At school the following day, Peter learns that Liz would be leaving for Oregon with her mother. The two say their goodbyes as her place as leader of the decathlon team is taken by the aloof and snarky Michelle Jones, or (as she prefers), "MJ".
Peter is summoned to the Avengers' new upstate headquarters by Tony, who wants to reward Peter for stopping Adrian by inducting him into the Avengers. Peter, however, doesn't feel ready to join yet and turns down Tony's offer. After Peter leaves, knowing there are reporters in the next room waiting for a big announcement, Tony decides to finally propose to Pepper Potts.
When Peter returns home, he finds a package left in his bedroom by "TS": his Stark Industries-made Spider-Suit! Unfortunately, Aunt May walks in just as he's finished putting it on.
In prison, Toomes is confronted by Mac Gargan, one of his buyers who was on the ferry. Gargan tells Toomes that there is a rumor that he knows Spider-Man's true identity, a factoid that he and some friends of his would like to know. Toomes denies the rumor, however; either out of respect for Peter, or a desire for his own vengeance...