This game is set 3643 years Before the Battle of Yavin (Star Wars: Episode IV: A New Hope).
In the years 7003-6900 BBY, a galactic conflict known as the "Hundred-Year Darkness" occurred (aka the "Second Great Schism"). It was essentially a civil war, as members of the early Jedi Order turned their backs on the Order's teachings and embraced the Dark Side of the Force. These were among the first of the Dark Jedi, who fought not only their former compatriots in the Jedi Order but also sought to seize control of the Galactic Republic.
The Dark Jedi were ultimately defeated and went into exile, venturing into unknown space. They found a planet called Korriban, populated by a species known as Sith. The Dark Jedi conquered Korriban and founded the first Sith Order, naming themselves the Dark Lords of the Sith. They remained in seclusion, away from the Jedi Order and the Galactic Republic, until 5000 BBY. During that time, they lost the hyperspace information necessary to return to Republic space, though they never lost their hatred for the Jedi. Over those nearly 2000 years, the Dark Lords had carved out a Sith Empire in that area of space unknown to the Republic.
In 5000 BBY, two civilian explorers from the Republic stumbled onto the Sith Empire at Korriban. The Dark Lord Naga Sadow used their arrival and subsequent imprisonment as a means to rise to power, claiming an impending Republic attack. The Sith Empire returned to "known" space to wage war against the Republic and the Jedi Order in a conflict known as the Great Hyperspace War. During this time, a Sith Lord known as Vitiate ruled over the planet Nathema. In the waning days of the war, as the Republic forces were chasing retreating Sith forces back into Sith territory, Vitiate called together a powerful group of remaining Sith Lords with the promise that he could save the Empire. He performed a Dark Side ritual on Nathema that devoured literally everything organic on the planet - people, plants, animals down to even insects. This ritual imbued in Vitiate immense Dark Side Force power, and has essentially allowed him to enjoy immortality ever since.
As the Republic forces battled the remnants of Sadow's fleet at Korriban, Lord Vitiate led an armada deeper into the Unknown Regions, fleeing the vengeful Republic. For twenty years they traveled, until they reached a long-lost world Sith world known as Dromund Kaas. Once there, the armada's journey ended, and Vitiate declared himself Emperor of the Sith Empire. For his part, Naga Sadow retreated to Yavin IV, where his few remaining Massassi slaves built many temples - including the one that the Alliance to Restore the Republic would ultimately use as their base of operations when the Galactic Empire's Death Star was destroyed, and where Luke Skywalker would found a Praxeum to re-establish the Jedi Order.
For more information on Vitiate, see Drew Karpyshyn's The Old Republic: Revan novel.