Despite his incredible strength, Godzilla has displayed a few weaknesses over the years. Early in the Showa series, he was vulnerable to electricity, though this weakness was apparently reckoned. Indeed, later films in the Showa series would portray Godzilla as being immune to electricity, or even drawing power from it.

In The Return of Godzilla, Godzilla was shown to be vulnerable to cadmium. Anti-nuclear bacteria has had an effect on him, though Godzilla's immune system was eventually able to overcome it. Later on, Godzilla is revealed to have a second brain in his spine, and Mechagodzilla was able to kill him by destroying it; however, he was revived by Rodan and further films seem to ignore this Achilles heel.

It was also suggested by the character Yuki in Godzilla vs. SpaceGodzilla that Godzilla has a soft spot under each armpit. However, the validity of this claim was highly dubious and this weak point was never exploited.

To date, the only weapon ever shown to be truly effective against Godzilla was Dr. Serizawa's Oxygen Destroyer, which disintegrated the king of the monsters down to the bone, and then into nothing. The technology for this weapon was lost forever when Serizawa killed himself along with the original Godzilla, in order to keep it from being used ever again.