Annihilus first appeared in Fantastic Four Annual #6 (Nov. 1968)
Many years ago, a race of beings know as the Tyannans travelled the cosmos, seeding planets with life-giving spores. During a mission in the Negative Zone to give it life, one of their ships suffered a freak collision from a meteor, causing it to crash-land on the nearby world of Arthoros. Before perishing, the crew of said vessel released their carried spores onto the surface of the planet. Years later, a descendant of one of these spores, a weak insectoid grew to exist among the created lifeforms. Instead of embracing its surroundings and fellow fauna however, the creature grew to be paranoid and aggressive, valuing its survival above all other things due to the overall harshness of Arthoros's volcanic environment. Eventually, the creature that came to be known as Annihilus, discovered the wreckage of the Tyannan vessel and (thanks to a mutation in the spores that granted it intelligence) was quick to master the technology that lay before it and eventually used said power to dominate and subjugate all other life on Arthoros, as well as threaten the other life-sewn worlds of the Negative Zone with invasion or outright obliteration.
Annihilus first encountered the Fantastic Four when they entered the Negative Zone seeking anti-particles needed to treat Sue's cosmic ray-related pregnancy complications. Annihilus' minions captured the heroes, but they escaped, stealing his Control Rod. They returned it after siphoning off the needed anti-particles and returned to Earth.
Annihilus was challenged by Janus the Nega-Man, a research scientist, who developed a module capable of harnessing antimatter energy within the Negative Zone. Annihilus defeated Janus, forcing the Nega-Man to lead him to Earth, but Janus was instead seemingly killed in the exploding atmosphere where matter meets antimatter. Annihilus nearly crossed over to Earth through one of Mister Fantastic's portals, but was driven back by the Avengers. Annihilus battled the Frightful Four, and once again attempted to escape the Negative Zone, but was foiled by Spider-Man and the Human Torch.
Sensing great power within Franklin Richards, Annihilus abducted him, along with the Fantastic Four, Medusa, Wyatt Wingfoot, and Agatha Harkness into the Negative Zone. He used a machine to prematurely release the child's full power potential, hoping to transfer the expended energies into himself. The Four defeated Annihilus and escaped back to Earth. Annihilus later allied with Mr Fantastic against the Mad Thinker.
Blastaar, a fellow Negative Zone warlord, stole the Control Rod and left Annihilus to die. Desperate, Annihilus tried to escape to Earth. He was defeated by the Avengers and Fantastic Four before returning to the Negative Zone. He was revived by Blastaar and regained his Control Rod.
Annihilus attacked the dimension of Asgard, home of the Norse Gods, but was repelled by King Odin. Annihilus later kidnapped a sleeping Odin, transporting him to the Negative Zone to steal his power. Annihilus was defeated by Thunderstrike.
Soon after, Annihilus and Blastaar joined forces with fellow Negative Zone warlord Syphonn. During a confrontation with Adam Warlock, Annihilus and Blastaar betrayed Syphonn, allowing him to be defeated.
Annihilus began leading the Annihilation Wave, an enormous fleet of Negative Zone battleships, ostensibly claiming to have the goal of conquering the universe. He claims that the universe is expanding into areas of the Negative Zone, making the universe now rightfully his territory. His forces destroy the Kyln, an intergalactic power station and maximum security prison, and the planet Xandar, headquarters of the Nova Corps. He allies with Thanos and two beings that were trapped in the Kyln by Galactus, Tenebrous, and Aegis. Tenebrous and Aegis defeat Galactus and the Silver Surfer, and the two are connected to a giant mechanism in Annihilus' starship. Annihilus' goal is actually creating a massive Power Cosmic bomb that will destroy the Universe and the Negative zone, leaving Annihilus the only survivor. Drax and the Silver Surfer manage to free Galactus, who destroys the Annihilation Wave. Nova battles and kills Annihilus.
Annihilus was reborn as an infant with all of the original's memories.
During the War of Kings, the Negative Zone is invaded by Darkhawk and his ally Talon. They discover the infant Annihilus and his Cosmic Control Rod have been placed under the care of a lesser lord of the Negative Zone, Catastrophus. Catastrophus had been using the Cosmic Control Rod to stunt the development of the infant Annihilus, hoping to prolong his own rule. Talon slew Catastrophus and seized the Control Rod, before calling out to the infant Annihilus and asking it to remember in the future that he had spared the creature's life.
During a later incursion into the Negative Zone, Johnny Storm discovers that Annihilus' forces have been rebuilt to "pre-Crunch assault levels," but are currently embroiled in a struggle with Blastaar's forces. Central to that struggle is a city built from the remains of the Negative Zone Prison Alpha. The war is further complicated by the involvement of the Universal Inhumans.
The Human Torch dies stopping a horde of aliens from the Negative Zone. Later, when Reed Richards opens a window to the Negative Zone and menaces Annihilus with the Ultimate Nullifier, Annihilus in return brandishes Johnny's uniform to Reed.
Annihilus uses regenerative surgery to revive the Human Torch, turning him into a gladiator when he refuses to reopen the portal from the Negative Zone.
Annihilus is contacted by an alternative version of Reed Richards (one of the last survivors of the Council of Reeds) via the Cult of the Negative Zone, a religious movement worshiping Annihilus. As part of a plan to orchestrate an event known as the "War of Four Cities", Richards offers to open a massive portal between the Negative Zone and Earth, allowing the Annihilation Wave to pass through. Annihilus agrees, and sends forces to attack the Baxter Building and secure its Negative Zone gateway.
Johnny Storm learns of the plan and enlists the Inhumans Light Brigade in an uprising, attacking Annihilus' forces as they prepare to cross over. With the aid of Light Brigade member Kal Blackbane, Johnny wrests the Cosmic Control Rod away from Annihilus, and takes control of the Annihilation Wave armada, using it to battle the Kree fleet as well as the Mad Celestials. Annihilus is captured and a leash is placed around his neck.
After a rebellion breaks out for free elections in the Negative Zone, Annihilus wins as a write-in candidate for new leader of the Negative Zone, with 14,980,336,901,214 votes for him.
During the Infinity storyline, Annihilus appears as a member of the Galactic Council.