Following the Mad Gear Gang's defeat in Final Fight 2, a gang war erupted in Metro City with the Skull Cross Gang eventually reigning supreme. Guy returns to Metro City following his training and meets with Mayor Haggar. The Skull Cross Gang then detonates a bomb and incites a riot in downtown Metro City, freeing their leader Marshal Black, from prison. Joined by female police officer Lucia Morgan and a mysterious street fighter named Dean, Guy and Haggar fight to take down the new gang of criminals. On the rooftop of the Skull Cross Gang's headquarters, Guy managed to defeat and kill Black by hitting him through the electric generator, ending their crimes.
- Ray/Billy - A basic member of the Skull Cross gang that attacks with a three-hit combo punch.
- Dirk/Rick - A typically weak punk from the Skull Cross gang. However, this particular member has Wolverine-like metal claws.
- Fat Jack/Arby - Football player-style Skull Cross member who comes running from one side of the screen to the other like a juggernaut.
- Hunter - A tall man that wears a hockey mask and baseball cap and walks in a hunched over, shuffling gait. He boasts a basic punch attack as well as a slide attack, but his most powerful attack is a slow, powerful swing from the baseball bat he keeps strapped to his back which can take out almost all of the player's health in a single strike.
- May - Female ninja-like Skull Cross member who slices with a kunai attached at her wrist. She will backflip out of harm's way when attacked.
- Fritz - Another one of those classic Final Fight punks that run by, tossing molotov cocktails and leaving a fiery mess in their wake.
- Dave - A renegade cop who has crossed over to the Skull Cross gang. Wielding a billy club, his deadliest attack is the Giant Jump. He is similar in appearance to Edi E. He was defeated by Lucia.
- Callman - The head waiter of "Creep Eats", a barbecue joint located in the back streets of Metro City. He was defeated by Lucia.
- Drake - This mad fisherman, dressed in a blue tanktop, blue jeans, a blue sailor hat and brown boots, attacks with a big anchor. He is in charge of the gang's weapon shipment from his boat "Sims". He was defeated by Dean.
- Caine - The gang's mechanic. Caine attacks the player with a gigantic wrench in an abandoned bus yard, but this large boss is nearsighted and slow-moving. He was defeated by Guy.
- Wong - This boss has a long ponytail with no other hair on his head. Wears a green cloth, brown shorts, brown boots, silver wrist guards, a brown strap to hold his top, and has a set of beads on his hand. He was defeated by Guy.
- Stray - Stray, the penultimate boss of the game, moves fast, jumping and striking with lightning speed. Armed with spiked knuckles, Stray wears a green trenchcoat with purple pants, gloves and a spiky mohawk. He was responsible for the slaughter of Dean's family. Dean defeated and killed him.
- Black - Black is the leader of the Skull Cross Gang and the final boss of the game. He looks very much like Fist of the North Star villain, The Colonel, with his clothes, red beret, scars and eyepatch, and borrows his jacket bursting action from the series main character, Kenshiro. He uses a flogging whip as his main weapon, occasionally throws knives, and possesses a spinning attack that is similar to Haggar's "Lariat", and a ki attack similar to Guy's "Palm Blast Attack".
- This was the first Final Fight game to feature four playable characters.
- Characters designs were handled by artist Bengus of Street Fighter, Darkstalkers and Marvel vs. Capcom 2 fame.