The first Giganto seen was one of the mutates created by the Deviant scientists to serve as part of Kro's invasion force when gathered on Monster Island. After Monster Hunters forced Kro to leave Monster Island, Giganto and the other Deviant Mutates found a new master known as the Mole Man and the Deviant Mutates live with him in Subterranea. The Mole Man unleashed Giganto upon the surface world to attack and destroy chemical plants in the Union of Soviet Socialist Republics, Australia, South America, and French Africa. It brought the attention to the Fantastic Four who headed to Monster Island. The Mole Man unleashed Giganto upon them until it was held back by the Human Torch's attacks.
A Giganto with a lizard-like appearance followed the Fantastic Four back to New York where it fought them. After it was knocked into the sea, that Giganto tunneled underground and escaped.
When the X-Men were in Mole Man's realm, the Mole Man unleashed Giganto upon them. Giganto was too much for the X-Men even when Mole Man sent more mutates to battle them. They were subdued in Mole Man's echo cave.
When Mole Man learned that millionaire Alden Maas had destroyed part of his underground kingdom when reaching the Earth's core, Mole Man unleashed Giganto upon Maas' facilities while he teamed up with Human Torch and Thing to fight Maas. Maas died before they arrived which denied vengeance from Mole Man.
When he believed that the Avengers were the ones responsible for destroying part of his kingdom, he unleashed Giganto and other mutates to attack Los Angeles. Iron Man intercepted Giganto and threw him into the sea while he and U.S. Agent had an attempt to decide what to do with it. When Giganto moved again, U.S. Agent tried to blind it with the afterburners on his skycycle only for Giganto to strike and U.S. Agent was separated from his vehicle. Wonder Man convinced Mole Man that the Avengers weren't responsible and blew his monster whistle to recall his monsters.
A Skrull named De'Lila was brainwashing Giganto and the rest of Mole Man's monster. Giganto was sent as a diversion while she looked for the lost Inorganic Technodrone. Giganto was used by Mole Men to capture Skrulls that were also looking for the Inorganic Technodrone. Giganto ended up fighting the "new" Fantastic Four (Spider-Man, Wolverine, Hulk, and Ghost Rider). It attempted to crush Hulk before it was stabbed by Wolverine. The Inorganic Technodrone was finally found by Giganto's mate who had laid on the flying saucer containing it thinking it was a nest. Although Mole Man and De'Lila tried to claim the Inorganic Technodrone for their own before it could end up imprinted by someone, it ended up accepting Giganto's mate who had imprinted on it and accepted it as if it were her own child.
Mole Man and Giganto were conjured from the timestream by Aron the Rogue Watcher to oppose allies of the Fantastic Four who have come to prevent him from creating a pocket universe. Giganto fought the Thing who buried it in a landslide.
Mole Man assembled Giganto and other monsters to invade the surface only for it to be abandoned when the Fantastic Four were discovered to be alive.
During his labors for the reality TV Show "The New Labors of Hercules," Hercules was sent to capture Giganto as a reimaging of his labor to capture the Man-Eating Mares of King Diomedes. Hercules used an enormous chain to snare Giganto then swung it at Giganto's brothers. Mole Man sent some Moloids to attack Hercules who attacked them by swinging Giganto toward them.
The Moloids later employed Giganto to help them find the Mole Man. To do that, they captured people dressed as Santa Claus when they misinterpreted Mole Man's last words being "Santa."
The second Giganto seen were a race of Altantean Beasts that resemble whales with legs. Their origins are unknown, but are said to have been genetically engineered by the Deviants. They sleep on the ocean floor until wakened/summoned by whoever blows the Horn of Proteus.
In the 19th Century, a Giganto encountered the Pequod and its crew led by Captain Ahab (who was Ulysses Bloodstone). This inspired the legend of Moby Dick.
When Prince Namor believed that the surface world was destroying Atlantis, he blew the Horn of Proteus to awaken a Giganto and unleashed it on the surface world. Mister Fantastic of the Fantastic Four attempted to slow it down with a smokescreen emitted by the Fantasticar, but was forced to withdraw when the Human Torch attempted to help and ended up having his flame extinguished by Giganto's blowhole attack. In order to destroy Giganto, Thing strapped a bomb to his back and walked into the monster's mouth and planted the bomb there. Giganto was slain by the explosion.
Later, Doctor Doom had one of his servants steal the Horn of Proteus awakening a larger Giganto and a number of sea monsters to attack a New England town. The Fantastic Four and the Avengers weren't able to stop them, but Reed Richards and Iron Man managed to attach a sonic generator on it causing the sea monsters to return to the sea.
Namor later summoned Giganto and other sea monsters to oppose Doctor Doom (who had amassed the combined power of the Cosmic Cube, Galactus, and a few other various objects/beings) and they weren't enough to defeat Doctor Doom.
Namor and the Fantastic Four fought Giganto when Captain Barracuda stole the Horn of Proteus.
In a plot to assist the Human Torch and Anne Raymond, Namor disguised himself as the Mad Thinker and unleashed a robot version of Giganto. The robot was burned by the Human Torch.
As a plot to ruin Namor, Llyra and Llyron used the Horn of Proteus to awaken Giganto and sent him to attack the UN Building. Namor was unable to defeat it and Llyron appeared heroic as Giganto returned to the sea.
Squirrel Girl managed to fight and defeat Giganto on one occasion.
The nearing arrival of the Apocalypse Beast caused Giganto and other monsters to go on a rampage in Tokyo. The Fantastic Four and Iron Man fought them. Human Torch and Thing took control of a robot called Oteksuken and used it to defeat Giganto and Eerok. When the Fantastic Four considered the sea monster Grogg that they will fight the Apocalypse Beast, Grogg led the sea monsters away from Tokyo.