Which Assassin's Creed game is the final chapter of the original Desmond Miles modern-day storyline?

Assassin's Creed III is the final chapter of the original Desmond Miles modern-day storyline.

The game continues Desmond's efforts against the modern Templars while he uses the Animus to experience the life of Ratonhnhaké:ton, commonly called Connor, during the American Revolution. Its modern-day plot reaches the major conclusion established across the first five numbered games.

Assassin's Creed Revelations, released before Assassin's Creed III, completes Ezio Auditore's historical story and concludes Altaïr's personal arc through connected memories. It does not end Desmond's modern-day narrative; that continuation belongs to Assassin's Creed III.

Assassin's Creed III was released in 2012. Its historical sections feature colonial North America and real figures such as George Washington, Benjamin Franklin, and Charles Lee, while its modern sections resolve the central Desmond conflict.