When Guile was a trainee in the United States Air Force, he befriended his superior officer, Charlie Nash and asked him to teach him in his unique form of fighting, which Charlie agreed to do. Guile learned the style, but his hot temper caused him to be not as proficient in the moves as Charlie was (shown in how Charlie can shoot Sonic Booms with one hand while Guile needs both.)
In the Street Fighter continuity, Guile was not introduced to the series until the events of Street Fighter Alpha 3, where he is addressed as "Commander". Guile is sent by the United States Air Force to look for his senior teammate and best friend Charlie, who has gone missing during a secret investigation. Guile's search eventually leads him to the Interpol investigator Chun-Li, who warns him not to follow Charlie due to the danger involved. Guile demonstrates his fighting ability, and assures Chun-Li that he will not let their friend come to harm. He eventually finds the Shadaloo base in Thailand. Guile informs Charlie that they do not need to be there any longer, as an aerial bombardment will begin in an hour. Charlie, however, insists that Bison will escape, and they come to blows. The sinister and powerful M. Bison appears and attacks the two Airmen, but is no match for their combined prowess. He is forced to retreat, calling a gunship to keep them pinned down and cover his escape. The two give chase, and follow him into the base, deciding that Bison's source of power, the Psycho Drive must be destroyed. Chun-Li then appears and informs them that the bombardment has been called off, surmising that Bison has somehow used his influence. She goes on to tell them that she has set explosives in an attempt to destroy the base, but is unsure if they'll be enough. As she rushes to escape, Charlie and Guile decide to set explosives around the Psycho Drive to ensure that if nothing else, it at least will be destroyed. As they set their charges, meanwhile M. Bison was fighting with Ryu and his allies in a epic battle, in the end Ryu defeated him destroying his body temporarily forcing Bison to regenerate in the Psycho Drive. Bison sucessfully regenarated his body then Charlie convinces Guile to escape while he holds Bison off, so Guile escapes right before the base explodes, with Charlie and Bison presumably caught in the blast. Chun-Li and Ryu eventually finds Guile standing on a mountain and says that Charlie may perhaps be alive somewhere, just as she believes that her father may be. Guile agrees, and says that he will continue to believe in Charlie.
Holding Bison responsible for the death of his best friend, he seemingly dedicates his whole life to exacting revenge on Bison, who has somehow survived the explosion. A court case against the Shadaloo dictator fails when Bison bribes all the judges to let him go free. Bison by this time wants revenge on Guile, Chun-Li, and many other people who had hindered his syndicate's efforts. To this end, he sets up the second World Warrior tournament to trap them, among other reasons. Guile, for his part, takes the bait, deserting his wife and daughter to pursue the vendetta.
Although the circumstances on how Guile approaches Bison is sketchy, he manages to force Bison into submission and asks him if he remembers him or his friend Charlie. While Bison admits that Guile is stronger than before, he ignores the question and dares Guile to kill him if he's so intent on revenge. Guile hesitates and relents, realizing that he should not become the murderer Bison is. What happens next (whether Guile attempts to take Bison into custody himself or whether he leaves him where he is for some reason) is not exactly known, but Akuma "kills" Bison with the Shun Goku Satsu shortly thereafter.
Guile returns home and visits Charlie's grave, admitting that no amount of revenge will bring him back. Suddenly, Julia and Amy show up, telling Guile that they are willing to forgive him if he is willing to come home. Guile is overjoyed and re-dedicates himself to being the best husband and father he can be.
Though his vendetta is concluded, Guile still believes it possible that Charlie may be alive, due to the fact that only Charlie's dog tags were found at the scene of the Shadaloo explosion, and demands that his superiors allow him to continue the search. His commanding officer refuses, and Guile tenders his resignation. Guile is surprised when his superior ignores the resignation, assigning Guile to the investigation of S.I.N., an organization with alleged ties to Shadaloo. Guile is at first incredulous that Shadaloo lives on without Bison, but soon takes to his new assignment with zeal. Recruiting Chun-Li to the investigation, the two enter a new tournament organized by S.I.N., in the hopes of infiltrating its headquarters. Over the course of the tournament he encounters a mysterious French fighter named Abel, who seems to recognize Guile's Sonic Boom attack. Since only he and Charlie know this attack, Guile comes to the conclusion that Abel has information on Charlie's ultimate fate, and immediately starts pressing him for answers on where he saw the Sonic Boom before. Abel is completely unwilling to share such sensitive information with a stranger who could easily be a spy, and they exchange blows. It is currently unknown who won the fight.
Later, in the S.I.N. headquarters, Guile recovers important data while Chun-Li is trapped by Vega, with the base's self-destruction imminent. En route to rescuing Chun-Li, Guile is ambushed by one of Bison's cyborgs (in the same mold as Seth). Abel arrives and takes on the cyborg instead, telling Guile where Chun-Li is and telling him to hurry. Exactly how Chun-Li is then rescued is unclear - Gen seems to have protected her from a collapse and then broken free from the rubble, but is nowhere to be seen later as Guile and Abel watch the base explode, with an unconscious Chun-Li in Guile's arms.
After these events, Guile returns to Charlie's grave, placing a beer bottle on it as a way of buying his old friend a drink. He tells the grave that although S.I.N.'s plans have been foiled, he knows that he hasn't seen the last of Shadaloo just yet.
Early Street Fighter II sketches and notes suggest that Guile was developed specifically to appeal to American fans. His physical appearance is strikingly different from the many Asian characters in the Street Fighter series, with light blue eyes, a chiseled jaw, and a particularly tall flattop haircut. The length of Guile's hair varies greatly from appearance to appearance. It is relatively realistic in Street Fighter II, and impossibly tall in SVC Chaos: SNK vs. Capcom. Capcom source books suggest that Guile's famous hairdo is styled with a special-order army hair spray to keep it up (though he ends up fixing it quickly after a match).
Another way Guile's image differs from the Asian combatants in the series is his flag of the United States flag tattoos on each arm, which is a retcon from the initial one he had in Street Fighter II artwork (due to sprites in most video games being forced to be symmetrical).
Finally, Guile's military fatigues complete his all-American look. The image of the uniformed American Airman is well-known in Japan due to the number of United States Armed Forces bases present in that country.
Guile wears Charlie's dog tag alongside his own, as he searches for Bison. In Street Fighter IV, Guile's alternate costume is Charlie's costume. Most fans note that he looks like the classic version of G.I. JOE character Duke.
Guile is quite tough, both physically and mentally. He has survived a lot, and is still standing, as well as still fighting). Although loyal to the military and the United States, Guile is extremely persistent. He is so driven to find out who betrayed him in the jungles of Thailand, and to try and get at M. Bison, that he would even put that over his duties. Despite this, he is a truly loving husband and father to his family.
Guile is generally considered a top tier character in the Street Fighter II series. He is considered by most players as the best character after Ken and Ryu. Guile is the first of many characters to introduce the "charge" gameplay style, in that a player must hold in a direction for a few seconds and press in the other afterwards to pull off a special move. This type of gameplay can make Guile a defensive character. Because of the short lag after his Sonic Boom, though, he can follow it and use his various forward-moving attacks to pressure the enemy, which makes him offensively very powerful as well.
Guile's two primary Special moves are the Sonic Boom (Projectile based attack) and Flash Kick (an anti-air attack). Both moves require a charge motion. Throughout the series, these have been Guile's main special attacks and has been known to have more Super Attacks than special moves. The "Sonic Hurricane" is not a projectile but if it connects, it traps the opponents in and does multiple hits. Double Flash is basically his Flash Kick with two more kicks added in. It acts like Ken's Shoryureppa in that it performs three Somersaults. It is also considered one of Guile's most difficult moves to perform. In Capcom vs. SNK he gained another Super Move called "Total Wipeout" which allows him to do consecutive punches that end with a final Backhand punch that knocks the opponent away. This move is similar to a super move he had in the EX series called "Opening Gambit", which also features consecutive punches but ends with a modified side Somersault kick instead of a backhand. His Meteor Combo in the EX series is called "Sonic Typhoon" which involves him shooting out a giant Sonic Boom tornado at his opponents, inflicting a heavy amount of damage. His Ultra Combos in Super Street Fighter IV are Flash Explosion (the Double Flash followed by one more kick to meet the opponent as they fall out of the air) and Sonic Hurricane.