Jörmungandr is the son of Loki and Angerboda, a giantess who was counted among his wives. Realizing the peril Jörmungandr could place Asgard in, Loki's father Odin banished Jörmungandr to the depths of the oceans of Earth.
The prophetess Volla prophecized that at the time of Ragnarok, the Midgard Serpent would be slain by Thor in battle, but then Thor himself would perish by the serpent's venom.
While in the court of Utgard-Loki, Thor was challenged to lift his cat off the ground, but was humbled when the cat managed to keep at least one foot on the ground at all times. Utgard-Loki then revealed his so-called cat was actually the Midgard Serpent in disguise.
Thor went fishing with an ox-head on the boat of the giant Hymir for the Midgard Serpent. Thor succeeded in catching the serpent, but Hymir grew afraid and cut the line believing he was saving Thor from himself. As the serpent retreated, Thor grew angry with Hymir and struck him. He then departed under the power of his hammer as he told Hymir he ought to be grateful that he was letting him live.
A scientist named Albert, while standing beneath a statue of the Midgard Serpent, saw tears dripping from its eyes. He collected the tears into a test tube and brought them back to his lab for study. He ultimately discovered that the tears were a universal solvent which could dissolve through anything—but this meant that he could not contain the solvent in anything, and it threatened to dissolve the Earth.
As Ragnarok seemed to draw near in Asgard, Hela brought the Midgard Serpent forth to launch an attack, and Thor found himself nearly powerless against it, having lost his hammer Mjolnir to Red Norvell. Norvell himself came to Thor's rescue, and fought the serpent all the way back to its lair, seemingly perishing in the process. When the serpent returned, Thor faced it again, now armed with Mjolnir; he managed to strike it down, and beat it until it vanished, bringing the seeming-Ragnarok to a halt.
As part of their scheme to overthrow Odin, Loki and Tyr captured the Golden Apples of Idunn and fed them to the Midgard Serpent, whom they found gnawing upon the roots of Yggdrasil.
To complete Odin's defeat, Loki had the serpent stretch itself to Earth so that his armies could follow Odin and those loyal to him. As they fought, the serpent wound itself around the Earth and began to crush it within its coils. Thor quickly enlisted the giant Hamir to assist him in baiting the serpent with an ox on a fishing pole. The serpent took the bait, and Thor dragged it free from the Earth and fought it. The serpent finally asked Thor to cease their fighting as they were evenly matched, and Thor agreed on the condition that the serpent return the golden apples. The serpent did so, and Thor then lashed it to Yggdrasil so that it could continue to gnaw upon its root.
Seeking the downfall of Thor, the Frost Giant Grundroth sought out the Midgard Serpent in the oceans of Earth, and used one of his men as bait to raise the serpent to the surface. The serpent took the appearance of the alien dragon Fin Fang Foom to communicate with the giants, and learned from them that Thor had been cursed by Hela to have old, brittle bones without the ability to heal his wounds. Seeing an opportunity to destroy Thor utterly in order to spare himself from death in Ragnarok, the serpent sought Thor out and came upon him in a park in Brooklyn. However, the serpent did not recognize Thor because of the armor he had donned to protect his damaged bones. Thor informed the serpent that he would oppose him, and the serpent responded that if he could lift one of his feet from the ground, he would face him in combat in a place away from innocent bystanders. Thor succeeded, and the two flew off to a secluded valley for combat.
There, the serpent dropped the form of Fin Fang Foom and appeared before Thor in its true form. At that instant, all time on Earth stood still. Thor then informed the serpent who he was, and swore to destroy him.
The two enemies engaged in a ferocious battle, during which Thor broke the serpent's teeth when it tried to swallow him. Finally, the serpent launched itself at Thor for its death strike, but Thor came back at it, unleashing the unfettered might of Mjolnir. The energies unleashed slew the serpent, while simultaneously reducing Thor's body to pulp.
Thor faced the Midgard Serpent in battle, but was quickly swallowed up. Unable to break free from its belly, Thor found himself exposed to the venom of the serpent's breath, and began to drift unconscious.
Thor was saved from death by Beta Ray Bill, who tore a hole through the serpent's stomach to reach him. The two hammer-wielders were able to smash their way out of the serpent's belly by combining the power of their hammers, and the Midgard Serpent faded back into Hel.
The Midgard Serpent was among the Asgardian menaces summoned to Earth by Morgan Le Fay to distract the Avengers while she abducted the Scarlet Witch. The Midgard Serpent surfaced in the South Pacific, where it was opposed by a team of Avengers led by the Black Widow.
As Thor lay defeated following his battle with Loki, the Midgard Serpent attempted to devour him, but Thor blasted it in the face with energy from Mjolnir as he teleported to Earth.