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Scarlet Helsing and Nilnewz dug him up, and he had Nilnewz turn Veronica into a vampire, after which Medlock, who was previously in love with Scarlet, fell in love with Veronica, which made Scarlet jealous. Medlock and Veronica attacked Betty when she found the amulet. However, Archie, Jughead, and Reggie killed Nilnewz to turn Veronica human again, and she used the amulet to turn Medlock old and toothless. The amulet was broken in the process, Scarlet and Medlock left together.
Scarlet was still in love with Medlock, but he betrayed her and drained her life force and youth to restore his power, casting her aside. He crashed Veronica's Halloween party in an attempt to turn her into a vampire again, as she was the ender who would stop Medlock's plans for the eternal night. Medlock turned Reggie into a vampire, ignoring Scarlet as he thought she wasn't worth the trouble. He turned Smithers into a vampire next, then Betty, then together they took Archie away, intending to use him as bait for Veronica.
Veronica, Jughead, Dilton, and Scarlet went to face Medlock, who had turned Archie into a vampire as well. Medlock attacked alongside Betty, Reggie, and Smithers. Jughead was able to temporarily subdue Betty by spraying her with garlic water, but Reggie took away his water blaster and Medlock turned him into a vampire, while Reggie turned Dilton. All seven vampires proceeded to turn Veronica into a vampire once more.
Medlock was seemingly triumphant, as him befriending the chosen one is the only way of bringing about the eternal night. However, the sun rose anyway, because Scarlet was the true ender, not Veronica. Scarlet opened a window, causing sunlight to shine on Medlock, destroying him. With Medlock's death, Archie, Jughead, Veronica, Betty, Reggie, Dilton, and Smithers were restored.
Medlock may have been inspired by The Master from Buffy the Vampire Slayer, as both are vampire leaders in a city full of paranormal activity, and Medlock is sometimes referred to as "the master". They also look similar.