The game does not feature either a manual saving or a checkpoint saving system, each individual level must be completed from beginning to end without the player dying or quitting. However, completed levels can be re-visited at any time from the level selection menu.
The player takes the role of Captain Frank Hayden, an elite Delta Force operative and the former leader of Black Saber, the President's personal black bag unit. Hayden and his team are attempting to recover a briefcase nuclear bomb code named "Red Mercury" from terrorist mercenary Vladimir Styanovich, known by his Nom de guerre "Vlady the Vicious", who is operating out of a coastal Syrian town. The team's Black Hawk is shot down immediately upon insertion, and they fight their way through the streets in pursuit of Vlady. Hayden is too late to stop Vlady from escaping via helicopter, but manages to damage the helicopter's rotors with small arms fire. Vlady, escaping over the ocean, states he is nobody's martyr, and attempts to disarm the nuke and "re-evaluate". However, to his dismay, the bomb re-arms itself seconds later. Vlady leaves the bomb on the helicopter and leaps into the ocean in a futile attempt to escape the blast. The blast wave from the nuke kills Vlady and capsizes the U.S. aircraft carrier which had been Hayden's base of operations, as well as destroying the helicopter sent to extract Hayden's team, knocking them unconscious.
The plot then moves to 72 hours earlier, with Hayden and his team on a mission in the Congo jungle to destroy a cache of Stinger missiles being used by local guerillas to shoot down American supply planes. After the successful completion of the mission, Hayden is picked up by Central Intelligence Agency agent Kate Daniels and Russian Foreign Intelligence Service agent Yuri Entropov, who recruit him for a mission. They have information that Vlady is prepared to purchase a Red Mercury bomb from a Russian research facility in Kazakhstan, and want Hayden to infiltrate the facility and eliminate Vlady and the Red Mercury bomb. Yuri mentions he has an agent on the inside who has provided this information. Hayden HALO jumps into the area and sneaks into the facility, where he witnesses the deal between Vlady and the facility's chief scientist. He recognizes Vlady as Wesley Holden, a former member of Black Saber who lost an arm on a past mission and still holds a grudge against Hayden as a result. Instead of the agreed payment, Vlady kills the scientist and escapes with the bomb. Hayden is too late to stop him, and discovers that Yuri's inside agent is Galena, a Russian spy who has a tumultuous past romantic history with Hayden.
Back at base, Kate is furious at Vlady's escape, while Hayden reveals Vlady's true identity as an American special forces operative. He learns that Vlady has two Red Mercury bombs, not just one. Galena reveals that the Red Mercury bombs can only be armed through a chemical process known only to a scientist named Boris in Chechnya. Hayden and his team travel to Chechnya to stop Vlady, but are once again too late. Vlady has Boris arm the bombs, then kills him and escapes, leaving behind a boobytrap for Hayden. Hayden next pursues Vlady onto a Lebanese freighter, but is yet again unable to prevent Vlady's escape. However, he learns that Vlady is heading to Syria, and pursues him there.
The plot than returns to the opening mission, and proceeds as before up to the detonation of the Red Mercury bomb. In the aftermath of the nuclear explosion, Hayden regains consciousness just as he is being retrieved by the captain of the aircraft carrier, who informs him that his team has been killed, and that Yuri and Galena have possession of the second Red Mercury bomb and are on their way to the G8 summit in Paris, France, while Kate also left the carrier to pursue them. Hayden realizes that Vlady was just a distraction for Yuri and Galena's plot to assassinate the G8 world leaders.
Pursuing them onto a high speed train bound for France, Hayden discovers that Galena is actually a hostage, and it is Kate who is the mastermind behind the plot to nuclearly impeach the world leaders, with Yuri as her partner. Yuri declares his motives as allowing Russia to regain her former glory, but is abruptly killed by Kate, who indicates their motives are not the same. Kate simply wants to "shake things up" by killing the world leaders, whom she views as ineffectual and corrupt, and reset the world back to its roots. Hayden and Galena set out to stop her, with Hayden fighting his way alongside French RAID officers through Paris under siege from Kate's elite Russian troopers. Hayden finally confronts Kate in a climactic showdown on top of the Eiffel Tower, with Kate attacking from a circling attack helicopter. Kate is eventually struck by gunfire and falls from the helicopter to her death, dropping the Red Mercury bomb in the process. Galena shows up to try and disarm the bomb; she succeeds in disabling the nuclear element, but the conventional explosives will still go off. Hayden and Galena successfully escape to the bottom of the tower just as the bomb explodes at the top. The two of them share a kiss as a crowd of Parisians cheers them on.