Assassin's Creed

Desmond Miles, a bartender, is kidnapped by Abstergo Industries. There, Desmond is forced to interface with the Animus, a device that is able to replay the genetic memories of the user's ancestors. In Desmond's case, they seek information about his ancestor Altaïr Ibn-La'Ahad, an Assassin during the time of the Third Crusade. Within the Animus, Altaïr's memories reveal that he was attempting to stop Robert de Sablé from taking an artifact from a temple, but broke all three of the Assassin Brotherhood's tenets in the process. The Brotherhood leader, Al Mualim, demotes Altaïr to the rank of Novice, and assigns him the task of assassinating nine people, all of whom are Templars, to regain his former status.

Desmond Miles is still trapped by Abstergo Industries (the modern-day face of the Knights Templar) after being forced to use the Animus device to revisit genetic memories of the Assassin Altaïr Ibn-La'Ahad, and has discovered prophetic warnings from Subject 16 (a previous captive) describing the end of the world. He is soon rescued by Lucy Stillman, a mole for the Assassins within Abstergo, who takes him to meet two other Assassins, historian Shaun Hastings and computer expert Rebecca Crane. They request that Desmond use their version of the Animus, dubbed the Animus 2.0, to relive memories of another Assassin, Ezio Auditore da Firenze, to train Desmond in the ways of the Assassins through the "Bleeding Effect" of the Animus.

After escaping the Templars' attack, Desmond Miles, Lucy Stillman, Rebecca Crane, and Shaun Hastings flee to Monteriggioni, establishing a new hideout in the ruins of the Villa Auditore. After restoring the electricity in the old tunnels under the villa, the player once again takes control of Ezio Auditore through Desmond's genetic memory, using the Animus 2.0 (which is the game's memory interface). Their mission is to find the Apple of Eden, an important and mysterious artifact that could prevent the impending disaster that is coming in that same year, believed to be perpetrated by the Templars.

present-day protagonist Desmond Miles has fallen into a coma due to the combined stress of being forced into killing Lucy Stillman and being controlled by Juno, the hologram attached to the Apple of Eden, a piece of Eden with hints of prolonged exposure in the Animus. While Shaun Hastings stays behind in Rome to attend Lucy's funeral, Rebecca Crane takes Desmond to New York and meets with his father, William Miles. In an effort to save Desmond's mind, the duo places him back in the Animus, though this time, in the machine's safe mode, known as the "Black Room."

Desmond, William, Rebecca, and Shaun find the Temple in a cave in New York and access it using their Apple of Eden. After partially activating the temple, Juno uses it to communicate with Desmond. Desmond is placed in the Animus where Juno's influence causes him to experience the life of his ancestor in 1754 England: the Templar Grand Master, Haytham Kenway. Haytham assassinates a patron at the Royal Opera House and steals a medallion; the Key to the Temple's inner chamber. Haytham is dispatched to the American Colonies to locate the Temple. While in Boston, he kills a slave trader, freeing a group of Mohawks including a woman named Kaniehti:io. She helps Haytham find the Temple in exchange for him killing General Braddock. Haytham and Kaniehti:io find that the Key is not able to open the temple itself. The pair develop a romantic relationship during their time together. The perspective then shifts to Ratonhnhaké:ton's childhood in 1760. His mother dies during an attack on his village led by the Templar Charles Lee. Years later, the village Elder informs a teenage Ratonhnhaké:ton that their tribe's duty is to prevent the Temple's discovery. The Elder gives him a transparent Sphere which allows Juno to communicate with him; she tells him of his importance and shows him the Assassins' symbol. The symbol leads him to the retired Assassin Achilles Davenport, who reluctantly begins training him as an assassin.

Samples taken from Desmond Miles' body in the moments after his death have enabled Abstergo Industries to continue to explore his genetic memories using the Animus' newfound cloud computing abilities. The unnamed player character is hired by Abstergo Entertainment to sift through the memories of Edward Kenway, an eighteenth-century pirate, the father of Haytham Kenway and the grandfather of Ratonhnhaké:ton. Ostensibly, this is to gather material for an Animus-powered interactive feature film, but in reality, Abstergo—the Templars of the present time—are searching for a First Civilization structure known as the Observatory, and are using the memories of Edward Kenway to find it.

The citizens were upset over the transition from French to Spanish control and Spain's new occupation within the city. However, in 1765, the French governor Jean-Jacques Blaise d'Abbadie made a negotiation with Templar Rafael Joaquín de Ferrer to stay as governor of New Orleans. This plot was later uncovered by the Assassin Aveline de Grandpré, who infiltrated the governor's mansion and assassinated him.