Since the Negative Zone is largely uninhabited, several would-be conquerors have attempted to bridge the gap to Earth and take over its population.

Spider-Man has also visited the Negative Zone, and acquired a costume that allowed him to merge with shadows and become practically invisible.

[volume & issue needed] A few months later after Spider-Man's name was cleared, Cassie St. Commons was given the guise of Dusk and joined the Slingers.

[volume & issue needed] The earliest origins of the Negative Zone and its culture have not been revealed, but estimates place its height of science and art over 1.5 million years ago, nearly coinciding with the rise of the Skrull and Kree races.

It is believed that around that time the Negative Zone ceased expanding and began its "Big Crunch", contracting toward a central nexus.

Tony Stark named it "Project 42", as it had been the 42nd idea out of a hundred that he, Reed Richards, and Hank Pym created following the Stamford Disaster.

In the one-shot Civil War: The Return, the Prison's warden was revealed as the first Captain Marvel, apparently back from the dead.

In Secret Invasion: Fantastic Four, the Skrull warrior Lyja (posing as Susan Richards) sends the Baxter Building into the Negative Zone.

A bit later, when the "new" Fantastic Four fly off to the prison, Franklin and Valeria are grabbed by Negative Zone creatures, but Lyja saves them.

[6] The Negative Zone is used to dispose of Earth-616's Galactus when he is accidentally transferred to the Ultimate Marvel universe due to the temporal distortions caused by the events of Age of Ultron.

[7] In Annihilation, the Negative Zone is visited by the Sentry, who is struggling to understand his new state of self and find a way to separate himself from the Void.

[17][18] During the Cataclysm event it is again established that there is in fact only one Negative Zone in the multiverse of Marvel Universe, with exit points to different realities and timelines, as the Ultimate Marvel heroes, after a brief trip to Earth-616 to acquire local information on Galactus,[19] eventually manage to send Galactus to the Negative Zone, reasoning that he will eventually starve to death because Negative Zone is made of anti-matter,[20] however, following an incident on Earth 616 where the Eternal known as Ikaris is brainwashed by a Kree device called the God's Whisper, the Eternals retrieve, with help from Aarkus, the comatose Galactus from the Negative Zone, and state that they plan to use the God's Whisper to unleash him upon the Kree when he awakens as revenge for what they did to Ikaris.

It has an atmosphere that is lethally acidic to humans and the Ultimate Fantastic Four, with the exception of the Thing, required space suits to live.

[24] In an alternate reality depicted in the 2021 "Heroes Reborn" miniseries, the Negative Zone is used by the Squadron Supreme of America to imprison Earth's most dangerous villains, such as General Annihilus, Doctor Juggernaut, the Hulk, Mister Beyonder, Namor, and Hank Pym / Ultron.