Sargon was a disembodied being – "matter without form" – among the last of a species of highly advanced humanoids who had evolved to a point where their mental powers had become almost god-like. When a cataclysmic war about half a million years ago ripped away their planet's atmosphere, Sargon and ten others chosen from both warring factions transferred their consciousnesses into spherical storage devices kept in a vault far beneath the surface. Sargon, his wife Thalassa, and Henoch, of the opposing faction, were eventually the only survivors – the other eight essences ceased to exist and their receptacles were dark.
In 2268, Sargon detected the USS Enterprise and summoned her to the planet. It had been his hope that the descendants of the colonies that his race had sown throughout the galaxy would one day venture into space. Sargon's request was that three crewmembers would temporarily relinquish their bodies to them so that they may construct android bodies as replacements. The one drawback was that the presence of such powerful consciousnesses in Human bodies accelerated the metabolism to dangerously high levels. Regular doses of metabolic drugs and close monitoring was required to enable the transfer to succeed. By mutual agreement of the Enterprise command crew, Sargon occupied the body of Captain James T. Kirk, while Thalassa occupied Ann Mulhall and Henoch took over Spock. While the bodies were occupied, the consciousnesses of the Enterprise crew were transferred to the aforementioned receptacles; their minds were too weak to interact with the outside world from there.
Henoch however wanted to keep his new Vulcan body since it was "accustomed to higher metabolism". He killed Kirk's body, hoping to kill Sargon with it. But Sargon deceived Henoch by fleeing his host and inhabiting the Enterprise herself. After Henoch was defeated and killed, Sargon and Thalassa realized that they did not have the control and discipline to use their mental powers in the physical realm. They left the Enterprise consigning themselves to 'oblivion'. (TOS: "Return to Tomorrow")
Sargon's disembodied voice was provided by James Doohan.
According to deleted lines from the final draft of the script (dated 15 November 1967), Sargon introduced himself as "Ruler of Lempal...once the most advanced civilization in this galaxy," and that "We were destroyed [...] two billion years ago."
In the original series blooper reel, Kirk is shown grasping Sargon's globe and exclaiming "Have no fear...Sargon is here!"