It introduces two giant, hairy humanoids called Gargantuas, which spawned from Frankenstein's monster from the previous film and are described as brothers.
The Green Gargantua is violent and savage, preying upon human beings; as he lives in sea water, he is given the name Gaira (ガイラ - from kai (or gai, for "stranger")), corresponding to Japanese characters for "sea"). The Brown Gargantua had been raised in captivity, and is docile and gentle; because he resides in the Japan Alps, called Sanda (サンダ, from san, "mountain"). The film follows the investigation and military engagements of these cres until their climatic confrontation in Tokyo.
From within the pitch-blackness of the ocean depths, a powerful green giant lurked. Armed with unquestionable strength and a bloodlust matched by no other, Gaira showed itself to be a murderous creature. Acting like the right hand of the devil, the ape like creature not only defeated the Giant Octopus, but attacked the very ship that the sea beast was just latched upon. Shoving the vessel beneath the waves, Gaira devoured most of the crew members that managed to flee the boat. Like rats from a sinking ship, they paddled their way through the waves. Unfortunately their efforts would be in vain, as the beast swam after them hungrily. But the monster's appetite called for more than just a few humans on the sunken ship, and Gaira made his way to land.
First arriving at an airport, the sea beast made its presence known to the mainland. After eating a helpless woman he snatched up, Gaira finally retreated as the sun pulled itself from the darkened clouds. Mulling over the destruction, the Japanese military went into action shortly after and set a trap for the beast. Waiting for the right time, the JSDF soldiers lured the creature deeper and deeper into the mainland. Electrified with over a million volts of power, the monster seemed to be dying, that is until his brother Sanda intervened.
Apparently the second offspring of the giant Frankenstein monster, Sanda was discovered as a child living in the forest by Doctor Paul Stewart. The creature was taken to a research laboratory where he quickly befriend one of the doctor's aids: Akemi. Though Sanda was affectionate toward his captors, he eventually escaped back to his mountain home, where he grew to enormous proportions. He would not reappear until a while later, when he rushes to the aide of his brother, Gaira who is under attack by the JSDF.
However, Sanda later discovers his brother does not share his compassion toward humanity, after catching him in the act of devouring some people. The brown giant attacks his brother in anger, driving him out of the forest. Gaira retreats straight to Tokyo, traveling through the dark waters of its harbor. Sanda follows his brother, and attempts to convince him to end his bloodthirsty ways. Gaira pays no heed and the two engage in battle destroying and leveling much of the city before dying in the volcanic aftermath.
- Several ambiguous references are made to Frankenstein vs. Baragon, but the only direct link between the films is the term "Frankenstein", which appears in the title and is used to refer to the Gargantuas ("Frankensteins") in the original Japanese dialogue.Due to dialogue referring to the monsters as "Frankensteins", Russ Tamblyn had to re-dub his dialogue for the American version of the film.
- The film itself is rather vague as to where (if at all) The War of the Gargantuas falls in regard to the continuity of Toho's other kaiju films, or even if it should be considered a canonical part of the Godzilla series. In 2002's Godzilla Against MechaGodzilla, however, specific reference to the Gargantuas is made, indicating that in this variation on Godzilla continuity, The War of the Gargantuas is considered by Toho to be a legitimate part of that Godzilla universe.
- An elder scientist discusses the fraternal relationship between the Gargantuas, and in the English dub refers to Cain and Abel. Dr. Stewart replies, "Brother against brother, huh? Sounds like some countries I know." A reference to the state of International relations in the time.
- Masers are used as weapons for the first time in a Toho film.
- US producer Henry G. Saperstein had planned to make a sequel where either Sanda, Gaira or a similar, new creature were pitted against Godzilla.
- The original ending of the film was to not only have Sanda and Gaila swallowed up by the new volcano, but the lava was to have spread to Tokyo where it was to destroy the city as well as the remaining cells of the monsters; cited in an interview with director Honda in Guy Tucker's Age of the Gods: A History of the Japanese Fantasy Film.
- Sanda (repainted suit with a new head) appeared in Yuke! Godman episode 16 Godman vs Sanda and the following year in Ike! Greenman episode 31 Greenman vs Sanda.
- Gaira (repainted suit with a new head) appeared in Yuke! Godman episode 17 Godman vs Gaira and the following year in Ike! Greenman episode 4 Greenman vs Gaira.
- Quentin Tarantino based the fight between Uma Thurman and Daryl Hannah in Kill Bill Vol. 2 on the final battle from The War of the Gargantuas. He showed his copy of the film to both actresses and told them he wanted it to be "The War of the Blonde Gargantuas."
- For the trailer of the upcoming TLC show Inedible to Incredible, music from the American version of War of the Gargantuas plays briefly in the background.