One single Flood spore can destroy a species
The first people to stumble upon them were the ancient humans, who lived over a 100,000 years ago. They were a technologic advanced race, rivalling the Forerunner sophistication from their home planet of Charum Hakkor. These space-dwelling prehistoric human found millions of glass canisters with an unknown, seemingly harmless, powder inside. Early testing showed the powder to be composed of short-chain organic molecules. In order to test out the powder’s effect on organic life, it was tested on Pheru, which had no immediate effect. However, the powder was in fact composed of Precursor genetic material, which was sent by them to destroy the Forerunners who had pushed them from their galaxy. Over time it began merging with and altering the genome of the Pheru in order to generate its own Flood Super Cells. Over time, the infected Pheru began to infect others and even began showing some symptoms of the Flood mutation, such as fleshy tentacle-like rods. Since Pheru were kept as pets by both humans and San'Shyuum, cross-species contamination was inevitable. The San'Shyuum and human alliance had been reigning for many years, both through trading as military.
Flight and Fight
Identifying the Flood as a major threat, humanity took up arms to rid the galaxy of any and all signs of the Flood. They named the threat ‘Flood’ since it spread so rapidly and consumed all life it encountered. The Human-Flood war ensued, which spread out over much of the Milky Way galaxy. Humanity tried to encapsulate the Flood as to better fight them, but the Flood spores were too fast. When humans found a Forerunner planet, they quickly took up arms to defeat the Flood that was present there.
This action unwittingly sparked the Human-Forerunner war, as the Forerunners thought the humans were attacking to expand their empire, but instead, they were running. The Human-Forerunner war was brutal, with the humans terribly outnumbered, but humanity still fought. The Human-San'Shyuum alliance fought valiantly, but in the end were overpowered by the Forerunners at their last stand on Charum Hakkor. As a punishment, humanity was to be devolved and completely annihilated as for a few 'seeds' for humanity to start over; the surrendered San'Shyuum's home world was put under quarantine for over 1200 years.
The Ur-Didact later regretted the complete destruction of Humanity, since, earlier, he was unaware the Flood was the reason for Humanity's aggression during the Human-Flood war.
The Flood had been attacking human forces from the rear, while the Forerunner assaulted them from the front. As humanities end approached, many of the Flood spores took over human spaceships as to slip by the Forerunner forces unnoticed. This worked, as these Flood ships reached the Forerunner world of Seaward. Finally realising the danger, the Forerunner took up arms against the Flood. During the 300-year-long Forerunner-Flood war many of the Forerunners were either killed or consumed by the Flood.
At first, the Forerunners would bombard a Flood-infested planet from orbit, but soon realised that was not enough. As the spread of the Flood continued, planetary bombardment after Flood infestation turned into complete system-wide destruction by detonating planetary system stars after a large Flood presence was detected in a Forerunner system. Meanwhile, the Forerunner started to take Flood into research facilities in order to search for a cure. Little did they know that the ancient human race they had just destroyed had found a cure, by altering human DNA and feeding massive amounts of people to the Flood, the Flood soon died and was nearly defeated. The last remaining Flood spores had gone into hiding and were biding their time, these spores were the ones that infested Seaward.
Hundreds of other unsuccessful methods were attempted by the Forerunners to overcome the Flood, and all possibilities were exhausted. After 300 year of devastating warfare, an end solution was devised, devices which were later known as 'Halo'. However, the Ur-Didact adamantly refused to activate the Halos, saying that it would overturn the Forerunners' pledge to preserve all life in the galaxy. When the Forerunners had no other choice, they detonated the rings, ending the war.
The Flood Reawakens
Thousands of years later, all of the Flood had starved, except for the Flood spores which were kept in the research facilities. Here, the Flood were protected from the Halo Array and would become active when they were set free. One such research facility on board Installation 04 was discovered by the Covenant Empire which unwittingly set the Flood free once again. At this point, humanity had once again reached the technology level to travel between star systems.
The Flood was loose once again, both the Covenant and humanity tried their best to stop the onslaught. In the beginning of the fighting, the Flood captured and 'interrogated' Captain Jacob Keyes. Keyes was fed to a Proto-Gravemind which read and destroyed Keyes' mind one memory at a time. Still able to fight it, Keyes did his best to hide sensitive information, such as the location of Earth from it. But before the Flood could reach this, Keyes was killed by John-117 and the most sensitive information was kept safe.
Later, the Flood took control of the human AI Cortana and gained massive amounts of data from it. The Gravemind then let Cortana guide John-117 to Installation 00 in order to take over the leading force of both the Covenant and humanity. This backfired however, when a nearby incomplete Halo Array was detonated which destroyed the Installation, with all remaining Flood present.
Flood had been defeated, a coalition of humans and the remaining Covenant was formed. Search parties were formed which were sent to rid the galaxy of any remaining Flood, specifically Forerunner research facilities, such as present on Installation 04.