The extra-dimensional beings known as the Possessors have captured Dr. Strange, Rintrah, Jack Russell and Topaz. The Lord Leader of the Possessors explains that after their previous defeat at Strange's hands much earlier in his career, he cast off his humiliation and rose to become supreme leader of his race. Then he planned to once again invade earth. They opened a portal to Colorado where they performed ritual cattle mutilation as sacrifices to bridge the two worlds.
The Possessors then inhabit the bodies of Strange, Rintrah and Russell, who transforms into the Werewolf. Topaz, already possessed by an alien spirit, repels her would-be Possessor and is kept prisoner. The Werewolf is forced to slay an awakening rancher whose body was host earlier to a Possessor, then they proceed toward a nearby town, terrorizing and possessing the citizens.
The Possessor guarding Topaz soon drops his rifle, and it becomes apparant to her that her captor is possessed by Strange's astral form. Shortly, they make their way after the Possessors, who are preparing the sacrifice several cattle, and throw wide open the portal from their world. Soon, armed townsmen arrive as well, but are kept at bay by the possessed Werewolf and Rintrah.
With the aid of the Eye of Agamotto, Dr. Strange casts out the Possessor inhabiting his body. His astral body back in his mortal shell, he creates a vortex that whips the Possessors back to their own dimension.
The townsmen now turn their attention to the Werewolf who runs but cannot evade their gunfire. Blinded by a brief flash of light, they witness the man-beast tumble into a gorge.
Farther away, Dr. Strange, Rintrah, Topaz and Jack Russell gather, having eluded the locals, who, in truth, saw an illusion of the Werewolf's death cast by Strange. Russell parts ways with the rest, and they return to New York, Topaz clutching a fistful of the Werewolf's fur that she will need to cast her exorcism spell.
Back-up story: "The Book of the Vishanti - Legacy of the Wolf", Part II" - Dr. Strange reads of how Werewolves came to be, and of the familial Russoff curse that now afflicts Jack Russell. In more recent times, the Caretakers, who genetically manipulated Men and wolves centuries earlier, had fought their creation, the warlock Daemond, Morbius and the psychic vampire, Tara, with Morbius the only survivor. The tale ends with the life story of Jack, from his eighteenth birthday to the present, when he's found a balance between his human and lupine aspects.