Re-living the assassin's life was only the beginning. Desmond Miles ultimately discovered the existence of the mystical Pieces of Eden by traversing through assassin Altaïr Ibn-La'Ahad's memories. However, this also revealed the global locations of the Pieces to the modern-day Knights Templar, Abstergo Industries. As a result of being trapped within the Abstergo labs and subjected to multiple treatments upon the Animus machine, Desmond became the victim of an extremely rare genetic blending disorder called "the bleeding effect." A notable symptom of this disease is Eagle Vision, characterized by the ability to visualize the incorporeal relationships between the self and external objects. As such, the bleeding effect paired with his natural curiosity led Desmond to discover a malicious plan behind Abstergo's corporate façade.
With the help of modern-day undercover assassins trained in Animus technology, Desmond escapes captivity from Abstergo, finds hidden shelter, and elects to re-enter the genetic memories of a more recent ancestor, Ezio Auditore da Firenze. Motivated by the knowledge that Abstergo is already searching for the missing Pieces of Eden within the modern day timeline, Desmond takes to Ezio's memories in order to uncover the locations of the rest of the Pieces. Through various trials, each of which increase the symptoms of the bleeding effect in Desmond's waking life, Ezio ultimately unlocks a hidden vault within Rome, believing to have found the hidden Pieces. However, he is instead greeted by a chamber empty of all treasures except a holographic goddess that illuminates the assassin to the lost history of creation, including the true origins of humans and a massive global catastrophe that almost eliminated all life on the planet. Soon after, Desmond awakes from the Animus and is told of an impending solar flare that may culminate in another catastrophe on December 21st, 2012.
After making another close escape from Abstergo forces, the modern-day assassins find new refuge within the Grand Temple, a long-forgotten fortress that was created by and had been infused with the advanced technology of the First Civilization. While exploring the temple, Desmond suddenly loses his identity and is forced back onto the machine as a sort of temporary treatment, whereby he dives into the genetic memories of an 18th century ancestor named Haytham Kenway. Kenway is not an assassin, however, but rather a Templar. After a series of events that led through multiple generations of lineage, Desmond manages to prevent the assassination of Commander-in-Chief George Washington of the Continental Army. In is waking life, Desmond regains his identity and begins to seek out small power sources that were designed to re-animate the ancient Temple. And once the power has been restored, Desmond is greeted with another holographic goddess, though this one is different from the goddess met by Ezio. This hologram informs Desmond that he has two choices for saving the world from the solar cataclysm: survival or sacrifice. The nobility of his bloodline wins out, and Desmond ultimately sacrifices his life for the sake of the planet.
Juno, now in the modern world but still within an etheric state, saves the planet from annihilation, but also has ulterior motives: the original humans were created as a workforce for the Gods, and Juno intends to restore the human population on Earth to its rightful place under her rule. Managing to transfer her consciousness to the 21st century Internet, Juno tried to influence humans – "her instruments" – in an endeavor to regain corporeal form. She was eventually successful at taking possession of a living human's body, but the human committed suicide in an attempt to eliminate Juno forever. But, rarely are goddesses so quickly defeated…
Having permeated every sub-sector of the Internet, both on-world and through local close-orbit networks, Juno easily rebooted her consciousness from one of many backups. However, experiencing corporeal death was excruciating, leading her to revise her previous strategy. She would not simply overtake a human host and walk onto the world's stage, but rather rebuild herself in a new fashion, using a combination of 21st century technology and her own inherent powers. As such, she has been quietly plotting her mission over the past two decades, watching how Abstergo grows as a powerful multi-national corporation, and subtly prodding the right individuals into executive leadership. Through patience and determination, she has reinforced her ties with the company in multiple ways, not the least of which is being an absentee member of the Board of Directors. This has left her with incalculable control over the future of the company, a future that includes biomimetic cytogenesis (that is to say, the replication of biophysical matter).
In another part of the world, a young lady comes home from college during a break between semesters, but the house is empty. Her parents are at work, and thus she has a few hours before they will all be reunited. In moments, she stumbles upon what she deems to be a futuristic recliner in the basement of the house. It's old and dusty, but she sits in it anyway and her consciousness is instantly sucked into an entirely different world, as if she is physically living within the 12th century (what we know to be Altaïr's time). She stumbles around in utter confusion and is quickly attacked for suspicion of being a mentally ill harlot. The shock of the situation desynchronizes her memories and she is thrown back into her waking life, straight into the furious gaze of her mother, Rebecca Crane.
Of course, Rebecca tells her daughter Chloe not to ever touch the machine again, and of course Chloe's curiosity gets the best of her. She finds a way to sneak in more time upon the Animus 7.0, and is this time thrown into a different era in the past, a Victorian age on the verge of the industrial revolution. She lasts a bit longer in these memories, holding her composure long enough to figure out who she is in that timeframe, but her youthful recklessness and lack of discipline keep forcing the machine to desync and reject her consciousness. Time rolls on and she becomes more adept at focusing her mind toward which era she wants to visit, as whom she wants to live. However, each trip onto the Animus begins to increase the symptoms of the bleeding effect, which influences the relationships within her waking life because she starts to see people's true motives. Moreover, every Animus trip triggers a ping signal through the Internet, which catches the attention of Juno due to its unmistakable frequency signature. Previously unseen for two decades, Juno becomes furious at the possibility of this new threat to her power.
One day, while Chloe was re-living the memories of a nurse during the first World War, a frequency inversion is initiated by Juno which causes the Animus to fry it's internal circuitry, with the potential to kill both machine and user. However, through the years, Rebecca had written a sub-routine within the Animus architecture to automatically re-write core, life-saving functions should a power surge destroy any element of the machine while in use. Upon sensing the frequency spike, the Animus initiates this failsafe, though it inadvertently re-organizes its code into a quantum structural framework, and thus initiates a temporal leap. Inside the machine, Chloe is participating in emergency battlefield surgery when the world suddenly re-arranges itself into a strange dystopian techno-ghetto Megapolis. And no matter how hard she tries to shake herself from the memories or forcefully tries to desync (short of death), she finds herself stuck in this new era. Her clothes and appearance have changed, and she manages to convince a skeptical onlooker to remind her of the year: 2258 A.D.
When Rebecca arrives home to find her daughter stuck within the Animus, she is enraged that her daughter disobeyed her, but notices that the settings of the machine have changed. Upon closer inspection, she is able to tap into the code to discover that her daughter is somehow able to access memories hidden within her DNA that have yet to temporally play out. In other words, the person whose memory Chloe is accessing has yet to be born. Dumbfounded, but cognizant of the evidence upon her monitor, Rebecca has no choice but to help find a way to release her daughter from the Animus.
Meanwhile, Juno convinces Abstergo's CEO Michael Winterborn to initiate the creation of a new sub-division within biopharmaceuticals, one specifically designed to create a whole human body from biosynthesis. They team up to present to the Board their idea: create a whole body that is devoid of conscious life. This is merely the integrative assemblage of individual body parts grown from stem cells. It would be a breakthrough in biomedical research, and the Board unanimously agrees. At once, the Prometheus Project is initialized.
Within the Animus, Chloe searches her person and discovers a futuristic form of communication: embedded within her forearm is a Bioluminescent Dermal Interface (BDI). The BDI is connected with the 23rd century's inter-planetary net, and Chloe soon learns how to operate its intuitive features. In seconds, she pulls up the ID of the person's memories of whom she is re-living. She is now someone named Terran 8146-7L, alias "TL". Moving on through the system on her arm, she pulls up a history of earth for the last two centuries, coming to find out that a company named Abstergo became the most influential corporation on Earth sometime around the end of the 21st century due to its groundbreaking biomedical research. So powerful was the company that it influenced all spheres of geopolitical decisions, culminating in a worldwide humanoid bioidentification program. Outrage had waved through the citizenry on all continents, but their respective governments quelled social revolution via unwarranted arrest now deemed legal through the lens of Earthland security. Uncooperative citizens were instantly targeted as traitorous outlaws, and those who did not comply with the rules of marshal law were incarcerated for terrorism. Within a decade, one quarter of the planet's civilized population was either arrested or killed in various uprisings. And the next two centuries saw a shift into totalitarian domination and military oligarchy. As such, all persons were re-designated by caste workforce, which leads Chloe to understand that the name Terran 8146-7L represents an Earth-based worker (Terran) from sector 8146 (a territory within the Federates States), compound 7-Lower level. Depressed and scared, she realizes that she has no choice but to live out the memories of TL for now, until she can find a way to de-sync and return to her real life.
In the present time, Rebecca is diving into the code structure of the Animus and discovers why the Animus is damaged. She finds the quantum coding, but thinks it better to leave it in operation while she tries to decipher the framework. Through a reverse step-wise process, she follows the original frequency inversion back to its place of origin, the Juno server dorms at Abstergo, Inc. Instantly, she realizes that Desmond may have sacrificed himself to save the planet, but it also freed Juno to dominate the world. Further, Juno must've realized that the re-activated Animus was a threat to her power, and thus she tried to permanently disable the machine. What Juno didn't expect, however, was Rebecca's coded failsafe. Thus, Juno may attempt to strike again, and Rebecca knows that she must find a way to isolate Chloe's consciousness from another frequency spike. And with a few more taps of the keyboard, Rebecca is speechless as she pulls up live first-person footage of the memories that Chloe is re-living.
Chloe, living in the memories of TL, will ultimately come to learn of her assassin heritage and begin training with an underground coup. They instruct her in all manner of tactical defense and 23rd century weaponry systems (e.g., hidden electron blades), eventually setting her on a series of missions to eliminate key officials within Abstergo, Inc. With these new abilities, she works her way through the corporation, assassinating figures and learning more about her ultimate target, the CEO Juno. Eventually, Chloe learns that Juno has been using the last Piece of Eden Apple since the 21st century to first control Abstergo, then multiple governments around the planet, culminating in domination over the people of Earth by implementing ubiquitous Internet access. The goddess' next mission is to begin controlling the inter-species colonies within the solar system, which is further motivation for Chloe to assassinate Juno. However, though Juno's consciousness is contained within a corporeal body, albeit one successively advanced since the Origin 1.0 body created by Abstergo in the 21st century, the CEO has been clever enough to create and hide multiple bodies and copies of her consciousness around the planet, should she be killed in some manner. Thus, Chloe must find and destroy all seven copies of Juno's consciousness, along with her core database. Once these are eliminated, Chloe manages to assassinate Juno, then sacrifices herself to set the last Piece of Eden on self-destruct, resulting in an explosion that destroys Abstergo, Inc.'s main starscraper headquarters in Washington, DC. Moreover, the resultant destruction sends an electroshock wave rebounding through the inter-planetary net, disabling all of Abstergo's controlling servers and freeing the citizenry.
The assassination of Juno in the 23rd century fully synchronizes Chloe's and TL's memories, and Chloe is released from the Animus. She speaks with her mother about everything that's happened, everything she's learned. Rebecca tells Chloe that Desmond is Chloe's real father, not Shaun Hastings, which is why Chloe can re-live memories of individuals who were intimate with Altaïr. Also, Rebecca reveals that she has kept the Animus around to re-live memories of spending time with Desmond, as that is all that she has left of him. They forgive each other and talk about TL's timeline, and what they can do in the present time to stop that future from happening.
Armed with the knowledge of Juno's plans, Chloe uses her skills to infiltrate Abstergo, Inc. in the present era. She finds the Piece of Eden Apple and uses it to free Winterborn and the Board of Directors from Juno's control. Once they are in their right minds, Chloe explains Juno's plans using Abstergo's own history of the Animus, and they agree to destroy the Prometheus Project. However, Juno will not go down so easily, and thus it will take Winterborn's help to seek out all of Juno's backup consciousnesses while Chloe takes the Piece of Eden down to the Biomedical facility. In the process, Juno finds multiple ways to slow their progress, but eventually the pair reach their respective destinations. However, Michael discovers that Juno's consciousness is not stored within Abstergo's servers, but rather embedded within the net itself. Thus, the only way to destroy her completely is to fry the entire Internet around the planet.
Yet, Rebecca reminds her daughter and Michael that goddesses are not constrained to linear time. As such, Juno must be eliminated from all conceivable timepoints simultaneously. Since the Animus is still operating under the quantum code framework, Rebecca quickly links the machine up to Abstergo's mainframe through an encrypted VPN, and instructs Chloe to tie the last Piece of Eden into the core servers at the corporation's headquarters. Afterward, Chloe sets the Apple to self-destruct. At the same moment that security breaks into Michael's office, the Apple explodes taking the entire building with it and sending a temporal electroshock wave through time, leaving Juno to scream into oblivion. Michael and Chloe do not survive, the Animus is destroyed, and the whole planetary Internet is fried in the process, eliminating the last 100 years of electronic technology from Earth.
Epilogue, Earth year 2037 A.D.: Rebecca and Shaun are standing over the grave of Chloe Miles, mourning her passing. For a moment, they simple stare at the tombstone, which is engraved with the insignia of the assassins and underscored by an epigraph: Lived wise, Perished free.
After a while, the pair is interrupted by a man in a black suit. "Excuse me, Ms. Crane, but the Presidents are awaiting your arrival in DC."
Rebecca nods silently, and soon her and Shaun are led to an executive car. As the vehicle drives away from Arlington, a series of futuristic buildings are under construction on the far horizon, architectural frames that seem to reflect those similar to the First Civilization…