The Amazing Spider-Man 2 is an action game released as a tie-in with the movie of the same name. It takes place outside the events of the film with a separate storyline where Spider-Man discovers a larger threat to NYC that has turned the underworld upside down, weaving together villains from the film and classic Marvel characters. The game opens with Spider-Man tracking down his uncle Ben's killer in order to bring him to justice. However, he soon finds that there is much more going on in the city of Manhattan and finds himself in a tangled web between Oscorp, Wilson Fisk and a mysterious new serial killer.

Players control Spider-Man in an open-world version of Manhattan similar to the previous games in the franchise. He can swing freely throughout the city using a web-swinging mechanic. The swinging has become more strict in the sense that it is no longer possible to always swing about anywhere if there is nothing present to attach it to, even though there are exceptions. The web is controlled with Spider-Man's left and right hand with two separate buttons. Pressing them together gives a boost. There are different types of web available, for instance used to freeze something or to make it explode. Different enemies need to be taken out with combat techniques and various upgrades can be earned throughout the game.

Similar to the inFAMOUS series there is a morale system where the player can choose to have Spider-Man intervene to stop crime or to ignore it. The existing crimes have been expanded with new types such as arson and hostage situations. Other types of activities include photo investigations, task force, aiding the police in a deadlock, rescue situations and infiltrating hideouts. Through the open-world design there are often multiple approaches, including stealth. There are also sections where Peter Park is controlled, doing detective work on foot. Peter's home acts as the main hub to replay missions, equip costumes and purchase upgrades. The in-game map is accessed through a mobile phone. It is also used to receive messages and access upgrades.