Colonel William F. Guile is searching for a killer, M. Bison. Reportedly, Bison was experimenting with a "psycho-drug" called DOLL, and experimented on Guile and Charlie's military unit in Cambodia, a bloody experiment which only Guile and his best friend Charlie (aka Nash) escaped. Charlie and Guile were sent in by the US military forces to bring in Bison, but Charlie was murdered by Bison (or one of his henchmen) in the second Alpha tournament. Guile has sworn revenge ever since, and has searched for Bison for many years since...

Guile left his family after being considered a loose cannon by the American military, and pursued M. Bison around the globe upon hearing of the second Street Fighter tournament. He immediately made an ally in the form of Chun Li, whom was also seeking revenge against the tyrant. But his quest for vengeance was cut short by a bloody beating by Sagat. Injured badly in a battle against Zangief, Guile was powerless to defend himself against the hulking juggernaut of Sagat. Guile was taken to the local hospital, where he and Chun Li were nearly killed by an assassin. Saved by Ryu, the two witnessed Ryu's battle with Bison and the toppling of his criminal empire...After the tournament, Guile found that his family had followed him to Thailand, and he was reunited with his wife and daughter at long last. His quest for venegeance was ended...