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The game begins with Elias telling his sons about the legend of how the Ghosts first appeared. Meanwhile in space, the Federation hijack the controlling space station of the Orbital Defense Initiative (ODIN), an orbital superweapon that utilizes kinetic bombardment, and use it to destroy several cities in the southwestern United States. The surviving American astronauts sacrifice themselves to self-destruct the space station and prevent the other ODIN satellites from launching their payloads further inland. Elias and the young Logan and David narrowly escape the destruction of San Diego.
Ten years later, the United States has fought the Federation to a stalemate along a front that comprises the destroyed cities, also known as "No Man's Land". Logan and Hesh are part of a US unit commanded by Elias and during a patrol, they spot an American working with the Federation who is called "Rorke". Soon after, the brothers are ambushed and rescued by members of the Ghosts who are seeking their companion Ajax, who was captured by Rorke. Logan and Hesh join the mission to rescue Ajax but arrive too late to rescue him and after he is killed by Rorke, they reunite with their father who reveals himself as the leader of Ghosts. Believing his sons are ready to join his unit, Elias welcomes them into the Ghosts and they learn from him that Rorke was once their leader. However, during a successful mission to assassinate General Almagro, then president of the Federation in the capital Caracas, Elias is forced to abandon Rorke, who was presumed dead, but instead turned traitor and is now hunting down his former companions.
The Ghosts track down and capture Rorke, but while flying back home, Rorke's men attack their plane and rescue him. The team then is forced to land deep into the Amazon Jungle where they witness a rocket being launched for an unknown purpose. Once reunited and rescued, the Ghosts storm a Federation laboratory in the Andes and obtain data regarding a classified operation in a factory at Rio De Janeiro. To secure a path to the factory, the Ghosts destroy the Federation's Atlas oil platform located in Antartica to lure the enemy fleet away from their objective and sink a destroyer guarding the Brazilian coast. Once inside the factory, the team discovers that the Federation had reverse engineered the ODIN's technology and developed their own orbital bombardment system. After destroying the factory, Elias and his sons regroup at a safehouse in Las Vegas but are captured by Rorke. After Hesh and Logan are forced to watch Rorke killing their father, the brothers manage to escape.
Realizing that once the Federation's ODIN becomes operational their defeat will be inevitable, the United States pool all their remaining forces in a synchronized attack to take down an enemy space center in Chile while a small team of soldiers boards a shuttle to take over the Federation satellites in space. Once both objectives are completed, Hesh and Logan pursue Rorke to avenge their father and are seemingly successful, only to find out during the aftermath that Rorke survived their battle. Logan attempts to defend his wounded brother, but has his arm broken and is kidnapped by Rorke, with the former Ghost announcing his plans to brainwash Logan into killing the rest of the team. In a post-credits scene, Logan is seen being kept inside a pit in the jungle, presumably going through the same torture methods that Rorke went through.