Yesterday Origins focuses on both the events that occurred centuries ago when John Yesterday became an immortal and the present timeline after the first game.
Having been caught by the Spanish Inquisition, John escapes with the help of Father Ginés. Ginés takes Yesterday to a noble estate, where he translates the Book of the Flesh in order to create the potion of immortality. When Ginés asks John to torture a child for the entertainment of the call, John refuses and helps him escape.
In the present day, John and his girlfriend Pauline sell a huge Japanese sculpture to Baxter, an eccentric millionaire heiress. While meeting her, John finds a book with the tattoo of the Book of the Flesh and tracks it to the author in New York. When leaving New York, John is kidnapped by Baxter's head of security and taken back to France, where he meets father Ginés, now old and decrepit, who only lives two or three weeks before dying and returning as a frail old man. Ginés begs John to read the book again to find a potion to reverse immortality. Baxter interrupts the process, planning to take the potion herself to become immortal.