Marvel's Avengers begins on the so-called A-Day, the day when Captain America, Iron Man, Hulk, Black Widow, and Thor unveil the new headquarters of the Avengers in San Francisco, equipped with the latest technology, as well as their new flying vehicle powered by a new experimental energy source.

From their flying base, players can take on Hero Missions (single-player) and Warzone Missions (co-op) at various sensitive locations around the world. Up to four players can team up online to defend Earth against increasingly dangerous threats that only the Avengers can face. The story unfolds over the course of many years, with each new superhero and each new region being added to the game at no additional cost.