During the events of Uncharted 2, Flynn meets Nathan Drake at a beach bar. Flynn asks Nate to assist him in stealing a Mongolian oil lamp previously owned by Marco Polo, which is located in an Istanbul museum. Flynn introduced Nate to Chloe Frazer as she will be the third helper for the plans they are organizing. Nate translates a page from Marco Polo's journal that Flynn "borrowed" from his employer, which outlines the importance of the lamp.
Flynn and Nate sneak their way through to the lamp's location in the museum, which Nate promptly smashes. Inside, it holds resins and a map, which reveals the location in which Marco Polo's fleet crashed centuries ago. Flynn takes the map Nate gave him, and proceeds to raise the alarm by shooting the pressure glass case that the lamp was held in. This leads to Drake's arrest and subsequent incarceration in a Turkish prison while Flynn escapes.
It is revealed that Flynn's employer was Zoran Lazarevic, a Eastern European warlord, who is trying to find the Cintamani Stone.
Throughout the events of Uncharted 2, Flynn manages to corner Nathan Drake numerous times, but always seems to fail at finishing the job due to his all-around ineptitude, and generally solves most of the clues leading to Shambala by capturing Drake and stealing them.
Flynn's path eventually leads him to the heart of Shambala, where he is betrayed by Lazarevic. He is found by Drake and his companions. Flynn then reveals a live grenade, courtesy of Lazarevic, which gravely wounds Elena and ultimately kills him.
It is implied that Flynn and Chloe had a relationship prior to the events of Uncharted 2. Flynn is a playable character in Uncharted 2's multiplayer, as part of the villain side.
On the multiplayer front, there are three Flynn skins to unlock on the side of the Villains, each unlocked when you hit a certain rank (but must still be purchased with your in-game cash). The different skins are:
- Default Flynn, with an olive-green shirt, is made for purchase at level 20.
- Heist Flynn, from the Museum chapter, is made available for purchase at level 20 also.
- Winter Flynn, from the final chapters during Tibet, is made available for purchase at level 30.
Through interviews, it was confirmed that Harry would also make a non-canon appearance as a character skin on the Villains side in Uncharted 3