As the Warehouse team prepares to celebrate the holidays in snowy South Dakota, Pete and Myka are called upon to hunt down a malevolent Santa Claus. Meanwhile, in time for Hanukkah, Artie and his estranged father, Isadore Weisfelt reunite after 30 years.

Pete Lattimer is hit in the head by an artifact and wakes up to a life where he was never born. Pete must hunt down and persuade the Warehouse team (none of whom recognize him) to go on this life or death mission with him to vanquish a long dead nemesis from the past to get everyone’s lives back.

While Pete and Myka travel to Las Vegas to investigate two deaths where the people inexplicably fell from great heights, Claudia and Steven investigate two jockeys in London who went into comas after winning their races. Meanwhile, Artie gets a visitor to the warehouse.

Pete and Myka capture Paracelsus but not before he makes himself immortal. When Myka's cancer becomes worse, Pete must make a deal with Paracelsus to cure his partner. Meanwhile, Claudia receives some startling news from Artie.

When Paracelsus takes control of Warehouse 13, it proves to only be the first step in his plan to recreate the entire world in his image. To stop him, Pete and Myka must follow him back through time to 1541 and prevent him from killing the Regents and becoming the permanent master of the Warehouses.

Pete's former girlfriend Kelly Hernandez asks him to help her find her missing grandmother, and the trail leads into a cancelled telenovela. Meanwhile, Artie forces Claudia to go with Steve to investigate the case of a college student of whose spine broke in the middle of a classroom presentation.

While the team deals with the news that Warehouse 13 is moving, Mrs. Frederic has them load their greatest memories of their missions into an artifact for future generations.