Modern Warfare 2 takes place five years after the previous installment. Gameplay is divided between the multinational counter-terrorist group Task Force 141, who are trying to eliminate Vladimir Makarov, and the US Army Rangers, who are defending against the Russian invasion of the United States. Several settings for the game include Afghanistan, Rio de Janeiro, Siberia, and Washington D.C.

Similar to previous installments within the Call of Duty series, the player assumes the role of various characters during the single-player campaign, changing perspectives throughout the progression of the story.

Each mission features a series of objectives that are displayed on the HUD, which marks their direction and distance. Tasks vary in their requirements, having the player arrive at a particular checkpoint, eliminate enemies in a specified location, stand their ground to defend an objective, or plant explosive charges on an enemy installation. The player is accompanied by friendly troops who cannot be issued orders. Laptop computers that contain enemy intelligence appear throughout the campaign and may be collected to unlock several game bonuses.

Modern Warfare 2 features a cooperative mode entitled Special Ops, which consists of independent missions similar in design to the "Mile High Club" epilogue mission from Call of Duty 4.These missions take place in a variety of locations from the campaign mode, but are not related to story of the campaign itself. Most of the Special Ops missions may be played alone, but support two player cooperative play,in which two players can play together locally or online. Such mode includes scenarios such as a snowmobile race between the two players, one player providing air support from an AC-130 with the other player conducting operations on the ground, capturing an enemy compound, and searching areas for and eliminating 40 or more enemies at a time.

Special Ops is divided into five separate groups of missions: Alpha, Bravo, Charlie, Delta, and Echo. Each mission may be played at three difficulty levels: regular, hardened, or veteran. Successfully completing a mission earns the players stars; there are up to three stars available for each mission: one star for completing the mission on regular difficulty, two for hardened, and three for veteran. Once enough stars are earned, more missions can be unlocked.There are a total of 23 missions, and 69 stars available for unlock. At the end of each mission, a statistics screen displays how long the player(s) took in order to complete the level and how many kills were scored, among other data.

The online multiplayer mode of Modern Warfare 2 retains the same experience points and unlockable reward system as that of Call of Duty 4, with game modes that include Free-For-All, Search & Destroy, Demolition, Domination, Team Deathmatch, and Capture The Flag.However, Modern Warfare 2 introduces several new features. Aside from new weapons, equipment, and perks that are now able to be upgraded to "pro versions",15 different kill streak rewards can be unlocked and selected by the player. Among these is the ability to receive a supply drop after achieving four kills in a row, order a Predator missile strike after five kills, and call in an AC-130 gunship to strike from the sky after 11 kills. Another new feature is the in-game host migration - if a match host leaves the game, the current game no longer ends (as is the case in Call of Duty 4), as a 'host migration delay' allows a new host to be selected and the game to continue on.There is also the addition of an optional third person mode which can be used in certain game types for multiplayer.