Vecna was originally a human named Henry Creel, later known as Subject 001 or "One" in the Hawkins National Lab experiments. He possessed extraordinary telepathic and psychokinetic abilities, which attracted the attention of Dr. Brenner. After revealing his true dark nature as a genocidal psychopath, Henry was overpowered by Eleven and banished to the Upside Down. Over seven years, the harsh conditions of the Upside Down gradually disfigured and transformed him into the being known as Vecna. He connected with and controlled the creatures within the Upside Down, forming a hive mind partly linked to the Mind Flayer, shaping it into a vessel to influence Earth. This transformation involved Henry becoming a mutilated, burned creature through exposure to the toxic atmosphere and abnormal lighting of the Upside Down. Before this, he was the first test subject at Hawkins Lab, where his powers were suppressed with a chip and replicated in other children. His story is a blend of his horrific past, his experiments at Hawkins, and his eventual rise as a malevolent entity ruling over the Upside Down creatures.

The original Dungeons & Dragons character Vecna, from which this version draws inspiration, was a powerful lich who achieved mastery over dark magic and was betrayed and destroyed by his lieutenant, leaving only his hand and eye as remnants. This mythos influenced the Stranger Things character's dark, magical, and haunting backstory but differs in specifics of origin and transformation.