Like its predecessor, the game takes place in a realistic and modern setting. The campaign follows multi-national special operations unit Task Force 141 and Mexican Special Forces unit Los Vaqueros as they attempt to track down terrorist leader, who is in possession of American-made ballistic missiles.

Call of Duty: Modern Warfare 2 has three different game modes: Campaign, Spec Ops, and Multiplayer. Campaign is a single-player mode where the player completes eighteen levels connected by an overarching plot.