The Negative Zone first appeared in Fantastic Four #51 (June 1966).
Essentially, it is a universe parallel to Earth's. The two have many similarities, but a few noteworthy differences include: all matter in the Negative Zone is negatively charged; the Negative Zone is entirely filled with a pressurized, breathable atmosphere; and near the center of the Negative Zone is a deadly vortex of unspeakable power. Since the Negative Zone is largely uninhabited, several would-be conquerors have attempted to bridge the gap to Earth and take over its population. A few notable residents of the Negative Zone include Blastaar, Annihilus, Stygorr and Noktiis.
The earliest origins of the Negative Zone and its culture have not been revealed, but rough 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 began "the Big Crunch," ceasing expansive progress and contracting to a central nexus. Some of the most powerful and influential races faced destruction and sought to preserve their lives.
One of the more aggressive races at this time were the Tyannans. The lion-like bipeds explored much of the Negative Zone, and eventually began to seed many of the planets, including Baluur, with their "spores of life." Their final mission, however, went awry.
A debris field had begun forming around Tyanna, which was at the very heart of the Negative Zone. The Big Crunch had begun pulling the universe back towards its center and planets crumbled under the increased pressure. One of the last remaining Tyannan ships careened off a large chunk of rock and crashed on the desolate planet of Arthros. The ship's engines dead and food processors destroyed, the Tyannan captain ordered the release of their life spores. Life slowly began to evolve on the planet, much as it did on Earth.
Farther from the core of the Negative Zone, other cultures thrived. One culture had gone so far as to cover half of their planet with a giant city, and then developed an artificial brain for it. The city, Ootah, even began to develop a sense of self-preservation and drove the inhabitants out of its boundaries, building up greater defenses to prevent them from returning.
Farther still from the core, the world of Kestor also flourished. It was the first recorded world beyond Tyanna that faced obliteration at the hands of the Big Crunch, roughly 10,000 years ago. Unlike Tyanna, whose gravitational force became greater than could sustain life, Kestor's sun was pulled toward the nexus. This caused the planet's several moons to shift their respective orbits and wreak havoc on the planet itself. As 20,000 beings left Kestor in a great space ark, the sun exploded with the fury of a supernova, substantially damaging their ship. All but 500 of the crew died and the navigational systems were destroyed, eliminating all hope of finding a new planet to call home.
One of the planets the Tyannans spored, Baluur, developed in a more barbarous manner. The inhabitants grew very large and powerful, and even the meek among them were stronger than an ordinary human. While they did progress technologically, their advances were at least partially driven by war. But they apparently began to experience the effects of the Big Crunch and several millennia ago they took their cities underneath the planet's surface. A sole entrance exists and is known only to the Baluurians themselves. They established a quiet monarchy and became very reclusive, only venturing into space on rare occasions.
Sentient life eventually developed on Arthros. A lone insect-like creature emerged from the primordial marsh 1000 years ago, and began to reason. A frail creature, he used his superior intellect to avoid larger predators and soon stumbled upon the Tyannan's derelict ship. Inside the craft, he donned a helmet in an attempt to warm himself. The helmet in fact had recordings of all the Tyannan technology and culture, and the creature was able to deftly assimilate all of it. He took the power from discarded life canisters and created a Cosmic Control Rod, capable of granting the wielder great power. Taking the name Annihilus, he set out to not only right those who wronged him, but to ensure that no one should ever harm him again.
While Annihilus forcibly took control of his immediate sector of space, a king rose to prominence on Baluur. Blastaar was a ruthless and powerful leader who sought to expand Baluurian domain. The other Baluurians feared him and were eventually able to depose him by sedating him heavily and sending him to what they hoped would be his destruction in the center of the Negative Zone.
While searching for a way to travel through sub-space, Reed Richards stumbled upon a gateway to the Negative Zone. He spent a fair amount of time studying it through probes, and determined that it was largely unpopulated. So much so, in fact, that he - and others - used the Negative Zone on several occasions to get rid of difficult enemies, such as the Mad Thinker's android, the Super-Adaptoid, and even Galactus. Reed and [The Fantastic Four](movie:34667) have since done more detailed explorations of the Zone and no longer use it to dispose of villains.