The story begins with Nathan "Nate" Drake (Nolan North) and Victor "Sully" Sullivan (Richard McGonagle) entering a pub in London to meet with a man named Talbot (Robin Atkin Downes), who is interested in purchasing Nate's ring. During the meeting, Nate and Sully accuse Talbot of offering them counterfeit banknotes, and a fight ensues. After fighting their way past Talbot's thugs, Nate and Sully emerge in an alleyway, where they are surrounded and subdued by Charlie Cutter (Graham McTavish), Talbot's cohort. They are then approached by Talbot's client, Katherine Marlowe (Rosalind Ayres), who steals Drake's ring. Nate attempts to go after her, but Cutter guns him and Sully down, seemingly killing them.

The story flashes back to 20 years earlier, where a teenage Nathan Drake (Billy Unger) explores a museum in Cartagena, Colombia, in search of Sir Francis Drake's ring, but is thrown out after guards suspect him of being a thief. Intrigued by the actions of Victor Sullivan, who he does not know at this point, Nate follows Sully to a keymaker and pickpockets him, before returning to the museum. He steals the ring, but before he can leave he is caught by Marlowe, her henchmen, and Sully, who was working for her. Nate flees with the ring, with Marlowe's agents in pursuit, but Sully rescues Nate from the agents and decides to act as a mentor to him.