The gameplay is roughly the same as in Mega Man: The Power Battle, as it keeps the controls, stages and weapon-copying. There are however several new additions. The playable characters are Mega Man, Proto Man, Bass and Duo, with Duo being a new addition to the cast. The four characters feature different attributes and abilities. When playing 2-Player, only one of the players can get the Robot Master's weapon.
As in The Power Battle there are three "stories" to choose from after; finding Dr. Wily, saving Roll, and recovering the stolen parts. All stories have different Robot Masters to fight, and halfway through it the player is given a different power-up. Unlike the previous game, The Power Fighters lets the player choose freely between Robot Master stages, and is given some hints on what the Robot Masters weaknesses are. Each of the characters can perform a special attack, which is executed by releasing a full buster charge while holding the joystick up. Megaman's special move, the "Mega Upper," is simply a jumping uppercut (like the Shoryuken); Protoman's special move, the "Proto Strike," allows him to shoot a massive, short-ranged burst of energy; Bass' special move, the "Crescent Kick," (Which is like the Flash Kick, another Street Fighter ability), lets him perform a somersaulting kick; Duo's special move, the "Giant Knuckle," is a standing uppercut that flings the enemy upwards (if the attack button is pressed again after the uppercut, Duo will jump up and slam the enemy down to the ground).