While working undercover for the Street Fighter operation, Guile gets contacted by Escher. Bison had just stolen a biological virus that can kill in 24 hours that he stole from Guile's old flame, Lucinda (or "Cindy"). Guile assembles a team consisting of Chun-Li, Ryu, Ken and Blanka, and heads to the jungle to put an end to Bison's schemes. Unfortunately both Ryu and Blanka contract the virus.

Bison commandeers a nuclear facility in China which is coincidentally situated near Chun-Li's birthplace which Bison had destroyed years prior. Guile assembles Blanka and Chun-Li for the mission to stop Bison. Chun-Li however, is only focused on destroying Bison and cares little weather the nuclear plant is destroyed. Eventually, Guile's scolding gets through to her and she lets Bison escape so that innocent people wouldn't be harmed.

Dee Jay relays to Escher and Chun-Li that he and Guile were ambushed by Bison and Zangief and that Guile was captured. Bison hooks Guile into a mind-probing device to find his Achilles heel, so he can reprogram Guile to destroy the rest of the street fighters. Meanwhile Chun-Li rallies Blanka, Dee Jay, Ryu and Ken to go to Guile's aid and infiltrate Bison's stronghold. After battling many mutants, the team rescues Guile and reminds him of the street fighter code: Discipline, justice, and commitment.

Sagat uses his vast army to wage war on the US embassy in Shadowlaw, all the while a young boy is trapped in the building while it's being evacuated. Blanka, Chun-Li and Guile head the rescue operation, but Guile also gets trapped in the building with the boy as well. Both Guile and his young friend try to escape Sagat's patrolling forces and were able to gain access to the secret computer files, which were very important apparently.

Bison steals a top secret military plane that can turn invisible at the push of a button so it's up to Guile, Dee Jay, Cammy and Blanka to get it back. They arrive on a mysterious island where Bison currently has set up shop, unfortunately Zangief is patrolling the area in a hovercraft. Dee Jay blames Zangief for ruining his fighting career, and they begin to fight while Guile fends off Bison. The Street Fighters eventually steal the plane just as the island explodes inexplicably.

Escher receives word that a new military laser was stolen by the female cyborg, the Satin Hammer and her cohort, T. Hawk. While T. Hawk was originally supposed to be undercover, Escher believes T. Hawk has switched sides. He charges Guile and Blanka to get to the bottom of situation. They eventually confront T. Hawk, who still maintains he's on their side, even though it's clear he's sympathetic towards the Satin Hammer. Eventually however, T. Hawk throws himself into Hammer's computer system which destroys it.

The millennium comet is on its scheduled 1000-year voyage in the skies over earth, but Bison uses his magnetic chi powers to redirect the comet towards the planet unless he gets a huge sum of money. Guile, Blanka, Ryu and Ken go the Himalayas to stop Bison, but the group gets separated. Blanka also meets Dhalsim while in the mountains, who he blames for turning him into a monster. With Dhalsim's help however, they stop Bison's plan and probably saved Ken and Ryu too.

A Street Fighter tournament is being held in India, and Escher sends Guile and the rest of the street fighters to compete. Bison is attending as well, and has a double threat of a plan; use his new mutant combatants to destroy the street fighters, or have Balrog create a video of the street fighters defiling a Hindu temple. Both Bison's plans fail when Guile saves a scientist then performs a flash kick on a bomb. This episode is notable for producing an Internet meme on Youtube ("This is delicious!" and "YESH! YESH!")

Word comes in that a scientist in Hawaii is concocting a serum that could help Blanka revert into his human form. Vega however, also hears of this serum and wants to use it to make himself eternally young. Vega captures the scientist and holds him for ransom. Blanka is forced to give Vega the cure, in exchange for the Doctor's life. Also, Blanka makes out with the scientist's assistant while falling from a plane. Vega drops the vial of serum too, losing his chance for immortality.

Ryu's cousin goes missing in Hong Kong while the street fighters are investigating a local drug operation. Action star Fei Long says he'll teach Guile the secrets of the city, if Guile teaches him how to use Chi energy attacks. Eventually, Ryu and Ken get captured by the drug runners. And it's up to Guile and Fei Long to save them.

A small city near Shadowlaw is in chaos as diamonds have been found to be rich in the region. Sagat and other warlords are lurking about, and each faction wants a piece of the pie. Guile is asked by Escher to check out the situation on behalf of the Street Fighters. Meanwhile Sawada has taken over Guile's former position in the AN and is currently in charge of the military presence. Hostilities run high as Guile as to defuse several bombs in the area, with the help of his Sonic Boom attack.

A mysterious warrior starts destroying both Bison's strongholds as well as those under Street Fighter jurisdiction. Both sides blame the other and it eventually comes down to Bison and Guile meeting on a Volcano for a final showdown. However, clumsy clues were given to both warriors which lead them to the location of the battle by none other than Akuma. Akuma wants both Bison and Guile to fight to death, where Akuma will then destroy the winner and steal their chi. Bison and Guile are forced to work together and eventually attack Akuma, only for him to escape via teleportation.