The Horus Heresy begins on the surface of Isstvan III with the Warmaster Horus' betrayal of the Loyalists in his own Space Marine Legion,
But the seeds of destruction for the Emperor's great dream had already been planted. One of the primarchs, Lorgar Aurelian of the Word Bearers Legion, had secretly turned to the service of the Dark Gods of the Warp approximately one hundred and sixty standard years into the Great Crusade. Seeking the true source of divinity in the universe after the Emperor had brutally reprimanded Lorgar and his Legion at the "perfect city" of Monarchia on the world of Khur for spreading the falsehood that the Emperor was the one, true god of Humanity, the primarch began a great pilgrmage across the galaxy.
Lorgar's quest eventually led the Word Bearers into the heart of the great, permanent Warp rift in the Segmentum Obscurus later named the Eye of Terror. There, Lorgar made contact with entities who he believed truly were divinities worthy of his worship -- the Chaos Gods. Devoting himself to their vision of seeing the Warp and realspace intertwined into a single reality and the benefits he believed this would bring to Humanity, the primarch spent the next four solar decades preparing to convert his brothers and their Legions to the service of Chaos.
To this end, Lorgar arranged for the Warmaster Horus to visit the barbarous world of Davin not long after the end of the Ullanor Crusade. There, he arranged for the Warmaster to be mortally wounded by a weapon tainted by the dark touch of the Chaos God Nurgle, the Plaguefather. Even a primarch's superhuman constitution proved incapable of defeating the Warp-tained pathogen created by the Plague God, and so to save his life Horus' own Astartes handed him over to a cabal of Davinite Chaos Cultists known as the Temple of the Serpent Lodge.
There, in a foul, sorcerous ritual that had been prepared by Lorgar and was overseen by the Word Bearers' First Chaplain Erebus, Horus' spirit was cast into the Warp, where the Chaos Gods promised to save his life if he would choose to become their servant and overthrow the rule of the Emperor of Mankind. Manipulating Horus' insecurities concerning the Emperor's affection for him and his unquenchable desire for recognition, power and glory, the Ruinous Powers succeeded in turning Horus against the Master of Mankind through a combination of lies and half-truths. With his agreement to their bargain, Horus' soul was returned to his body in the Davinite temple and he awoke fully healed, though he now walked the path of damnation.
Over the next few standard years, Horus began to surreptitiously move all the pieces of the Imperial military he commanded into place to launch a grand rebellion against the Emperor's authority that was intended to result in Horus claiming the Throneworld of Terra and the mantle of Humanity's new emperor. The Warmaster, always with the aid of Lorgar and his Daemonic allies, managed to suborn the loyalties of eight of his brother primarchs.
He did this by exploiting their own insecurities concerning the Emperor's treatment of them and the jealous rivalries that many of the primarchs had developed over the course of the Great Crusade with their fellows. Horus' promises of greater political autonomy and the removal of restrictions on the acquisition of certain technologies forbidden by the Emperor also won the allegiance of Kelbor-Hal, the fabricator-general of Mars and leader of the ancient Mechanicum.
By 005.M31, the treason of Horus, known in later centuries as the "Horus Heresy," spread to embrace approximately half of the Imperium's military forces, including small Planetary Defence Forces, many regiments of the Imperial Army, the 9 Chaos Space Marine Traitor Legions and nearly half of the ancient Mechanicum's potent Taghmata forces, Titan Legions and Knight houses, forming the core of Mechanicum adepts who chose to serve the Ruinous Powers and were later called the "Dark Mechanicum", though they referred to themselves as the "True Mechanicum."
The Horus Heresy truly began at the world of Isstvan III, where Horus used the outbreak of a Chaos-fuelled rebellion against Imperial rule as a pretext to send all of the Loyalist Astartes -- those Space Marines who Horus and his allied primarchs knew would never turn against the Emperor -- to the surface. Once the Loyalists of four of the Space Marine Legions allied to Horus were planetside and engaged in combat, the orbiting Imperial fleet unleashed a devastating bombardment of virus bombs upon them, seeking to kill all of the Loyalists as well as the entire planetary population in what is remembered as the "Isstvan III Atrocity." But Horus miscalculated, for several of the Loyalists learned of the plot beforehand and were able to warn their battle-brothers on the surface of Isstvan III before the deadly barrage began. Thousands of Loyalist Astartes survived, forcing Horus and the Traitors to launch a solar-weeks-long campaign of grinding urban combat against their former allies as atmospheric occlusion caused by the virus-bombing prevented a simple orbital bombardment of their positions. At the same time, another group of Loyalists aboard the Death Guard Legion frigate Eisenstein managed to flee into the Warp with news of the Warmaster's betrayal, intending to let the Emperor know of the treachery of His favorite son.
After Horus finished off the Loyalists on Isstvan III with an orbital bombardment once the skies over the target area had cleared enough to allow a precise orbital assault, he moved his forces to the neighbouring world of Isstvan V to await the Imperial retribution he knew would come. The Loyalists rightly believed they outnumbered Horus' four Space Marine Legions and so when the Emperor, represented in the matter by Rogal Dorn, primarch of the Imperial Fists Legion and the Praetorian of Terra, sent a force of seven Legions against him at Isstvan V, the Loyalists thought the Warmaster's rebellion would prove short-lived.
But they had deeply underestimated the man the Emperor had chosen to take His place at the head of the Imperium's military machine. Of the seven Legiones Astartes sent against him at Isstvan V in ca. 006.M31, Horus had already secretly gained the allegiance of four, who abruptly turned on the three Loyalist Legions and destroyed them almost to an Astartes. In a single stroke, at the so-called "Drop Site Massacre" of Isstvan V, Horus had nearly doubled his forces and weakened those of the Loyalists to the point that he could now begin a drive on Terra itself.
The terrible civil war that ensued as Horus drove towards the heart of the Imperium lasted for a further 7 standard years, killed trillions of men and women across the galaxy and culminated in 014.M31 in a massive assault upon the Imperial Palace during the climactic Siege of Terra. After 55 solar days of fighting, the war was ended by the Emperor and Horus duelling in single combat aboard Horus' flagship, the Gloriana-class Battleship Vengeful Spirit, in orbit of Terra, before further Loyalist reinforcements could reach the Throneworld and throw the Traitor forces back from their prize.
Although mortally wounded during the final battle with His once-favoured son, who had become immensely powerful and swollen with the energies of the Warp as a result of the united favour of the Chaos Gods, the Emperor was able to strike down Horus using the full gathered might of His unrivaled psychic powers. Despite His great sorrow and reluctance, the Emperor obliterated Horus' soul from the Warp, preventing him from being resurrected to serve the Ruinous Powers once more.
Without their leader, the unity of the forces of Chaos soon crumbled and as Loyalist reinforcements led by Roboute Guilliman of the Ultramarines arrived in the Sol System, the Traitor Legions and their Dark Mechanicum and mortal allies retreated to the massive Warp rift in the Segmentum Obscurus known as the Eye of Terror.
At His own direction, the crippled body of the Emperor was installed into the cybernetic life support mechanisms of the psychic amplifier known as the Golden Throne. This allowed His mind to have an anchor in realspace from which He could battle the influence of the Chaos Gods in the Warp and continue to direct the energies of the Astronomican, the psychic beacon that was the lifeblood of the Imperium's communications, commerce and interstellar travel.
In a postscript to the terrible traumas of the Heresy, a battle between Loyalists and Traitors fought on the planet of Sotha, home to the ancient Necron Warp beacon known as the Pharos, drew the attentions of the hive fleets of the Tyranids to the galaxy. It was in this ancient time that their vast biomechanical fleets first began to move across the extragalactic void towards the Milky Way Galaxy, drawn ever on by the shining psychic beacon of the Astronomican.