A Russian ultranationalist by the name of Imran Zakhaev is determined to return his homeland to the Soviet times. Zakhaev knows the United States of America would never allow this to happen, thus he funds a coup in the Middle East, organized by his ally Khaled Al-Asad, to draw attention away from Russia.
In the Prologue levels, players take the role of Sergeant "Soap" MacTavish in his initiation into the SAS. The players will meet the members of the SAS squad and go through a basic tutorial of the game play, which includes a time trial in a mock cargo ship set up. The player will then proceed on a mission to intercept the real cargo ship in the Bering Strait alongside Captain Price and Gaz. In the cargo hold, the SAS team finds a nuclear warhead draped in a flag with Arabic writing. The ship is subsequently attacked by MiG's, with the SAS team barely escaping from the sinking ship. Players will then switch roles with President Al-Fulani of an unknown Middle Eastern country as he is executed by Al-Asad.
In Act 1, MacTavish and an SAS team rescue a Russian informant code-named "Nikolai". While escaping with Nikolai, their helicopter is shot down, and they then flee from Ultranationalist search teams. Later on, the player takes control of the gunner of an AC-130H Spectre gunship that provides fire support for Captain Price and the surviving SAS members. Meanwhile, in the Middle East, Sergeant Paul Jackson, Lieutenant Vasquez and Staff Sergeant Griggs fight their way to the capital city of the country Al-Fulani was executed in. They first attack a television studio where they believe Al-Asad is broadcasting, but it turns out to be a recording. They then rescue a stranded Abrams tank called War Pig. Their efforts culminate in a massive assault upon the capital. However, a nuclear weapon is detonated, killing Jackson and Vasquez. Griggs is not present during the detonation.
In Act 2, MacTavish is tasked with finding and capturing Al-Asad. However, when it is found out that Zakhaev is supplying Al-Asad, Al-Asad is executed by Price. There is then a flashback mission where Captain MacMillan, a sniper team leader, and then Lieutenant Price are sent in to the first assassination mission issued by the British government since World War II. Their target, Zakhaev, then a rich Ultranationalist, is shot, but only his arm is lost. Back in the present, the squad evacuates the town on the Sea Knight "Big Bird", which has Griggs on it. Then, Soap and his SAS team, Griggs' Marine squad and Sgt.Kamarov's Russian Loyalists attempt to capture Victor Zakhaev, Imran Zakhaev's son for information. However, just when the strike force corners Victor, he commits suicide by shooting himself in the head to avoid capture.
In Act 3, MacTavish and his SAS squad, joined by an American sniper team and an American Marine squad, attempt to retake a launch facility recently captured by the Ultranationalist. Price knew Zakhaev was outraged by the death of his son and would threaten to launch ICBMs at the US. They first rescue Griggs after he misses the landing zone and then they knock out the power to the ICBM facility so the Marines can breach the perimeter. Then they meet with the American sniper team, but two ICBMs are launched at the US Eastern Seaboard, which could cause 40 million casualties. They enter the facility and after retaking it and aborting the launch, MacTavish, Gaz, Price, Griggs, and some other squad members escape in Russian cars. The Ultranationalists pursue them and an enemy helicopter damages a bridge vital to their escape. The men crash, stranding the squad without support. After a tanker explodes, all of the squad members are incapacitated, except Griggs, and Zakhaev comes to the bridge to observe. Griggs is shot in the neck while trying to drag MacTavish to safety and Gaz is executed by Zakhaev. When Zakhaev is on the verge of killing Soap, a Loyalist Ml-28 destroys the Hind and distracts Zakhaev long enough for Price to toss MacTavish his M1191.45, which MacTavish uses to kill Zakhaev and his guards. Russian Loyalists come to aid the men, evacuating MacTavish and attempting to revive Price, who appears to be dead when the medic attempting to resuscitate him becomes frustrated. A television news report is played mentioning the events of the game, but the newscaster dismisses the events as "struggles" and "nuclear missile testing", stating that the real events of the past six days were unknown to the public.
In the Epilogue, a bonus mission can be played titled, Mile High Club. This bonus mission is seemingly unrelated to the plot. In it, you (the player) take the role of an unnamed SAS officer (possibly "Soap"), and must eradicate all terrorists currently occupying a double decker airliner, while safely securing a hostage VIP.
