Guile joined the United States Air Forces and quickly became close with his superior, Charlie Nash, who eventually taught him his fighting style. Charlie goes missing during a secret mission, prompting the Air force to send Guile to find him. While investigating the case, he comes across Chun-Li, an Interpol agent, who advises Guile to drop the mission.

He would find Charlie inside a Shadaloo base. It is here that Guile learns of M. Bison and his plan. Charlie convinces Guile to chase off after Bison to discover his power source, the Psycho Drive, even if a bombardment by the Air Force is near. Chun-Li is then able to hold off the bombing of the base and ensure they can escape and reach Bison.

They don't manage to get to him, but they reach the Psycho Drive and wrap it in explosives to guarantee its destruction. Bison, meanwhile, is confronted by Ryu and killed to then regenerate inside the Psycho Drive. Charlie tells Guile to leave. Charlie then holds off Bison from escaping, making sure he and the Psycho drive are caught in the blast of the explosion. After Charlie's presumed death, Guile makes sure Bison and his cronies pay it.

From then on, Guile joins forces with Chun-Li and works on dismantling Shadaloo. But even with the organization gone, many of its agents still bring up chaos to the world. After years of hoping that Charlie is alive, Guile seeks to resign from the military. A request that was denied by his superiors, who place him on a new mission, this time against S.I.N, an organization related to Shadaloo

While in his new assignment, Guile comes to know, and even fights, a man named Abel, who has a similar fighting style to Charlie. After defeating him, Guile brings him back to base for interrogation, believing he might have information about Charlie's whereabouts. Alas, he had no information to give.

Still, Abel would become a close ally of Guile and Chun-Li as they worked on eliminating the remaining cells of Shadaloo.

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