Col. Guile, Chun-Li Zang, Charlie Blanka, Ken Masters, Ryu Hoshi and others form an elite group of street fighters from all around the world to combat General Bison and his henchmen, attempting to stop his evil dreams of world domination.
While working undercover for the Street Fighter operation, Guile gets contacted by Escher. Bison had just stolen a biological virus from Guile's old flame, Lucinda (or "Cindy") and that the virus itself can kill an infected person from within 24 hours of instant contact. Guile assembles a team consisting of Chun-Li, Ryu, Ken and Blanka, and heads to the jungle to put an end to Bison's scheme. Unfortunately, both Ryu and Blanka contract the virus and that the group must race against the clock in order to get the antidote needed to save their friends.
Bison commandeers a nuclear facility in China, which is coincidentally situated near Chun-Li's own birthplace which Bison had destroyed years prior. Guile assembles Blanka and Chun-Li for the mission to stop Bison. However, Chun-Li is only focused on getting her revenge against Bison and cares little whether 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 himself was captured. Bison hooks Guile into a mind-probing device to find his Achilles heel so that he can brainwash and reprogram Guile into destroy the rest of the Street Fighters. Chun-Li rallies Blanka, Dee Jay, Ryu, and Ken to help rescue Guile and infiltrate Bison's stronghold. After battling many mutants, the team saves Guile and reminds him of the Street Fighter code: Discipline, justice, and commitment.
Sagat uses his vast army to wage war on a U.S. embassy in Shadaloo, 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 gets trapped in the building along 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 some 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 and 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 back 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 in order to monitor the Satin Hammer's activities, Escher believes that T. Hawk has switched sides. He charges Guile and Blanka to get to the bottom of the situation. They eventually confront T. Hawk, who still maintains that he's on their side, even though it's clear he's sympathetic towards the Satin Hammer. Eventually however, T. Hawk throws himself into the Satin Hammer's computer system and destroys it in an instant, even though the Satin Hammer manages to escape capture from him and the others.
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 and threatens to rip apart the continent of the U.S. through the comet's own crash unless he gets a huge sum of money. Guile, Blanka, Ryu, and Ken go the Himalayas to stop Bison, but the group gets separated by an avalanche. Blanka meets up Dhalsim while in the mountains and blames him for his monstrous appearance. With Dhalsim's help, Guile and Blanka manage to stop Bison's plan while saving Ryu and Ken from within the process.
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 false video of the Street Fighters defiling a Hindu temple. The mutants are introduced at the tournament with Toccata and Fugue in D minor. Both of Bison's plans fail when Guile saves the captured scientist and performs a Flash Kick on a time bomb. This episode is notable for producing an Internet Meme on YouTube (Bison's phrase of "This is delicious!" and his enthusiastic shout of "YES! YES!" as he sees Guile being defeated)
Word comes in that a scientist in Hawaii is concocting a serum that could help Blanka revert into his human form. Vega 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 from within the situation, losing his only 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 show 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 Shadaloo is in chaos as rare diamonds have been found to be rich in the region. Sagat and many other warlords are lurking about as 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 Allied Nations (AN) and is currently in charge of the military presence. Hostilities run high as Guile manages to defuse several bombs in the area, with the help of his Sonic Boom attack.
Bison finally gets captured at the hands of Cammy's former British teammates, MI5. While the world thinks that Bison's capture is the first step to Shadaloo's destruction, Bison's supporters randomly start blowing up locations in England and threatens that it will continue until Bison is released, along with a 2 billion pound payoff. Zangief places bombs in a specific chunnel that connects a train track between England and France, so it's up to Guile, Dee Jay, Honda, and Cammy to prevent the tunnel's destruction.
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 island 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 himself. Akuma wants both Bison and Guile to fight each other 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. Despite Bison and Guile's reluctant teamwork, Akuma is able to escape via teleportation and that both Bison and Guile decide to postpone their own battle and head their separate ways, much to the shock of their own teammates. This episode contained a lot of deformed animation, making this a lot more cartoony than other episodes