Following the events of Assassin's Creed: Revelations, series' protagonist Desmond Miles and his assassin allies have traveled to the Grand Temple of "Those Who Came Before", an ancient race of powerful beings who created humankind before a global calamity thousands of years before the events of the game made them almost extinct and ravaged the Earth. To find the key to activate the temple and prevent the imminent recurrence of the global disaster in 2012, Desmond uses the Animus, a device that allows him to view the memories of his ancestors, to explore the life of his 18th century ancestor in Colonial America during the American Revolution; a young, half-English, half-Mohawk man named Ratonhnhaké:ton, also known as Connor, whose father is Grand Master of the Templar Order in the colonies. Connor is caught up in the Assassins' conflict with the Templar order when his Native American village is attacked by the Templars, who intend to seize control of the newly forming country.
Connor's story spans two decades of his life, from his childhood in 1760 to 1783. Boston and New York are cities that can be explored, as well as the American Colonial Frontier, spanning forest, cliffs, rivers, Connor's Mohawk village, and the settlements of Lexington, Concord and Charlestown. The player can hunt small and large animals, and approximately one third of the story takes place in the Frontier. The city of Philadelphia can also be visited at one point during the game, as can The Caribbean during several naval missions. The entire Eastern seaboard is also explorable via Connor's captaining his naval warship, the Aquila.