During the opening days of the invasion of Afghanistan, Tier 1 operators of a Navy SEAL squad from DEVGRU, call sign Neptune, composed of operators code-named Mother, Voodoo, Preacher and Rabbit are sent to meet with an Afghan informant named Tariq, who has intelligence that the CIA is interested in retrieving. Neptune is ambushed by Chechen forces, and fights their way through the village to recover Tariq.

The game opens at an undisclosed ship dock in Karachi, Pakistan. Task Force Mako is the newly designated team consisting the previously known U.S. Navy SEALs of Mother, Preacher, and Voodoo, who are assigned by DEVGRU to sabotage a black market arms deal, involving with an Al-Qaeda linked jihad movement.