Awakened by nuclear testing like Godzilla, Anguirus was first sighted battling the other monster on the remote Iwato Island. The monsters dove into the sea and resurfaced in Osaka to resume their battle. Godzilla managed to fatally wound Anguirus before lighting his foe ablaze with his atomic breath, killing the Ankylosaurus kaiju. Anguirus was Godzilla's first ever opponent as well as the first monster he ever defeated. Despite this Anguirus' demise at the hands of Godzilla, a second one would appear in the coming years and befriend Godzilla.

When pilot Shoichi Tsukioka landed on Iwato Island to rescue his friend and colleague Koji Kobayashi, the two men discovered Anguirus and Godzilla locked in battle on the island. The two monsters eventually tackled each other into the ocean, and disappeared. The pilots reported their story to the authorities in Osaka, who determined that Anguirus was a creature that lived alongside Godzilla in prehistoric times, and like Godzilla had been reawakened by nuclear testing. The JSDF enforced a blackout on the city and used flares to draw Godzilla away, but when a group of prisoners escaped from a prison bus as it was evacuating, they led the police on a high-speed chase that ended with a gasoline truck crashing into a refinery and starting a huge fire. This fire quickly spread and drew both Godzilla and Anguirus into Osaka, where they resumed their battle. The monsters tore apart the city as their battle reached Osaka Castle. Godzilla tackled Anguirus into the building, then bit down on his opponent's neck. Anguirus roared out in agony as he began to bleed profusely, and was thrown into a moat by Godzilla. As Anguirus attempted to stagger back to his feet, Godzilla unleashed his atomic breath, incinerating his foe and leaving him victorious.