Super Godzilla is a 16-bit Godzilla game where the player can take control of Toho's famous big green lizard as they rampage through Japan. The game is divided into two main gameplay modes, Movement and Battle. Movement has the player travel through the city using the D-pad and a map located on the bottom of the screen with the objective being to destroy certain objectives such as enemy humans and buildings as well as pick up power-ups. There is an animation in the screen above the map that shows the results of their movements and attacks.

Battle mode kicks in when the player locates an enemy on the map, like Biollante or Mechagodzilla, and is taken to a side-scrolling cinematic-style battle where the player must use punches, tail whips and the famous fire breath to drain the energy of the opposing monster. However, the Fighting Spirit system is present which is in a sense a morality meter where the player must pick the right attacks at the right time in order to connect certain attacks. Choosing the wrong attacks or failing to connect with them will cause the meter to drop and make Godzilla more vulnerable to attack.

When King Ghidorah suddenly attacks Osaka, the military deploys the Super X II to locate Godzilla, and they use a transmitter to control the mutant dinosaur. Godzilla is led to Osaka, where he fights and kills King Ghidorah. Immediately afterwards, Ghidorah's body vanishes and an alien spaceship appears. The invaders reveal that they were controlling Ghidorah, and demand that the human race surrender. Meanwhile, another Godzilla appears in Mt. Fuji, and the Super X II lures the real Godzilla there to fight it. Godzilla confronts the new Godzilla, who is revealed to be Mechagodzilla wearing an artificial skin. During Godzilla's fight with the robot, the aliens kidnap Dr. Shiragami and take him to Lake Ashino. Godzilla goes there to rescue the professor, and is confronted by Biollante, his plant-like clone. After defeating Biollante, the Super X II rescues Shiragami, it is revealed that the doctor had recovered DNA samples of Godzilla and King Ghidorah and had been experimenting on them to create a serum that enhances the physical attributes of any being. However, the aliens invaded his laboratory and stole the samples, using them to create Biollante.

Dr. Shiragami injects some of the serum into Godzilla, making him stronger. The aliens unleash Battra in Yokohama, and it lays an egg that is threatening to hatch. Godzilla travels to Yokohama, kills Battra, and destroys the egg before it can hatch. King Ghidorah soon returns as Mecha-King Ghidorah, having been resurrected by the aliens, and begins to attack Yokohama. The aliens reveal that they have hidden several capsules around the city that are holding Shiragami's serum. If Godzilla can find them all before Mecha-King Ghidorah destroys fifty percent of the city, he will mutate into a more powerful form. He succeeds, and confronts Mecha-King Ghidorah. The cyborg monster is easily outmatched by Godzilla's newfound power and is destroyed. However, the battle is far from over. The aliens travel to China, where they awaken an ancient creature called Bagan and inject him with sample of the serum, making him just as powerful as Godzilla. The two titans battle in the ruins of Yokohama, and Bagan proves to be more challenging than all the other monsters he faced. Eventually, Godzilla bests Bagan, and the aliens retreat, but not before promising revenge. The serum eventually wears off, and Godzilla returns to his original form. The Super X II disables the transmitter, releasing Godzilla from their control, and the mutant dinosaur returns to the ocean with humanity indebted to him for his aide.