Skeletor is the main antagonist of the Masters of the Universe franchise, and is the most evil being and most dangerous threat on Eternia. His only goal is power, and to that end he will not rest until he possesses the secrets of Castle Grayskull, whereby he could become master of the universe. This places him in direct conflict with the only man powerful enough to stop him, He-Man.

The character was initially presented simply as an evil demon from another dimension, and in general his origins were not as important as his evil motives. However, the introduction of Hordak as Skeletor's former teacher provided a brief glimpse into a past. Near the end of the original Masters of the Universe franchise, it was hinted that Skeletor might have once been Keldor, the brother of He-Man's father, King Randor. The development of Skeletor's backstory as a dashing, ambitious villain played heavily into his characterization in the 2002 relaunch of the franchise.

Skeletor was one of only a handful of characters that carried over to The New Adventures of He-Man brand, which sent He-Man to the far future to help the Galactic Guardians save the last of humanity from the Evil Mutants. Skeletor follows his enemy, and offers his services to the Mutants simply because he must rid the universe of He-Man.

In the original 1983 series, Skeletor is still the main antagonist, and as the Sorceress of Castle Grayskull calls him, a demon from another dimension, Infinita. He is a cruel warlord who rules the dark side of Eternia from Snake Mountain with an iron fist. His title is Evil Lord of Destruction. He learned black magic from Hordak, the powerful warlord of Eternia's sister planet Etheria, of whom he was once the second-in-command. In the animated movie "The Secret of the Sword", it is revealed that Skeletor betrayed Hordak, who had abducted Princess Adora after his forces were defeated, by telling The Sorceress and Man-At-Arms the way to Hordak's secret base. Following the Horde's retreat, Skeletor set himself up in Snake Mountain, and in the episode Golden Disks of Knowledge it is revealed that Skeletor himself built Snake Mountain (which in the 2002 series was portrayed as originally being King Hiss' base of operations).

Skeletor's portrayal in the series is generally comical, as the show's writers were forced to use villains mainly for comic value to keep the show suitable for young children. While he had a genuinely sinister personality in the beginning, as the series progresses Skeletor is treated as more and more incompetent, often bordering on a pantomime villain. However, several episodes still show the greater extent of Skeletor's evil, such as "The Problem with Power" in which he tricks He-Man into thinking he has killed a man with his own power, knowing that He-Man will exile himself in shame for his mistake.