Desmond Miles was born in one of the Assassin Order's hideouts in South Dakota known as "The Farm" an off-the-grid compound with a population of about, less than one hundred people. Though he was destined to be trained as an Assassin, he was frustrated by his parents' explicit instructions not to leave the compound and believed them to be overly concerned and paranoid. On his 16th birthday, he finally fled, wanting "to see the rest of the world."
After leaving the Assassin compound, he went into hiding for nine years. While keeping a low profile, he eventually became a bartender. Aware of the Templars, and wanting to avoid both them and the Assassins, Desmond never used his real name and used only cash to purchase items. However, he was eventually found, traced through a fingerprint needed for a motorcycle license, and was kidnapped to be brought to an Abstergo facility in Italy.
Desmond is forced into Abstergo's Animus, a machine that allows him to relive the memories of his ancestors stored in his DNA, by scientists Dr. Warren Vidic and Dr. Lucy Stillman, employees of Abstergo Corporation. They explain that they are searching the memories of Desmond's ancestors, specifically Altaïr ibn La-Ahad, for a certain piece of information, which they refuse to disclose. Desmond agrees and put into the Animus. Later on, after recovering the information for which Vidic was searching, Abstergo's executives' order Desmond killed; Lucy's quick thinking saves him, and she persuades Vidic to keep him alive until they know for certain that he's of no further use. Upon returning to his room, Desmond discovers that the Bleeding Effect has given him Altair's 'Eagle Vision', allowing him to discern friend from foe and read cryptic messages left on the walls and floor by Subject 16, another Animus subject.
Assassin's Creed II
Desmond escapes from Abstergo with the help of Lucy, Who was revealed to be an undercover Assassin. Shortly afterward, Desmond is taken to Lucy's Assassin's hideout, and he goes into another Animus, supervised by Lucy and her team, consisting of Shaun Hastings and Rebecca Crane, in order to be quickly trained as an Assassin via the bleeding effect. This time, he goes into the memories of Ezio Auditore da Firenze, an ancestor from the Renaissance.
After successfully navigating Ezio's early memories (with help from Shaun Hastings and Rebecca Crane monitoring him), Desmond is extracted from the Animus to avoid the mental degradation that Subject 16 suffered as a side-effect of the Bleeding Effect. Shortly after extraction, Desmond flashes back to one of Altaïr's memories, despite not being linked to the Animus. Here, Desmond learns of Altaïr having a lover, Maria, a Templar used as a decoy by Robert de Sable. As Altaïr leaves, Desmond wonders why he isn't following the Assassin; instead, he moves towards Maria, where he enters her womb, showing that Altaïr's child (and another of Desmond's ancestors) has just been conceived.
After spending more time in the Animus 2.0, Desmond begins to adjust to his newly developed skills, becoming highly agile and an expert in whatever weapons Ezio learned to use. The last segment of Ezio's memories brings an astonished Ezio (and by extension, Desmond) to a futuristic chamber underneath the Vatican, where a goddess, Minerva, addresses Desmond by name and, through Ezio, warns him of an impending cataclysm that has the potential to destroy all life on Earth. Desmond is pulled from the Animus quickly afterward after Abstergo discovers their hideout. The team escape, Desmond using the skills acquired from the bleeding effect to help fight off Abstergo's forces. Desmond enters the Animus while in transit, knowing that Ezio or perhaps Subject 16, may have the answers they seek.
Assassin's Creed: Brotherhood
Two weeks have passed and Desmond, Lucy, Shaun, and Rebecca arrive at Monteriggioni, where Villa Auditore was located. They set up a safe house in the Villa's sanctuary, and Desmond re-enters the Animus, in order to discover the location of the Apple of Eden, an artifact obtained by Ezio and one of the "Pieces of Eden". After finding the location of the Apple through the Animus, Desmond and the others learn that the Apple is hidden under the Colosseum. The assassins find a way inside an ancient Vault, where the Apple is located. He then takes the Apple and Juno begins to talk to Desmond and takes control of his body and forces him to stab Lucy for reasons which are unclear. After Desmond passes out, he gets put back into the Animus by William Miles and an unknown man, who are assassins. The events and assignments for the assassins seem to end after this and Desmond falls into a coma.
Assassin's Creed: Revelations
After Stabbing Lucy, Desmond Fades into a Coma and is plugged into the black room to keep him alive and find a way out. Upon waking up, he finds Subject 16 in the black room, telling him he must explore his ancestors remaining memories and separate all of his ancestors memories from his own to be able to survive, Desmond Explores Ezio's days in Constantinople, talking with Subject 16 along the way, soon when the animus tries to delete Desmond, Subject 16 sacrifices himself for Desmond so he can save himself. Desmond achieves the Sync Nexus, receiving a message from Ezio and the first civilization telling him to go to the Grand Temple. Desmond then wakes up from his coma, saying he knows what they need to do.
Desmond Holds a serious view on life due to being raised as an Assassin since birth and not getting to see the rest of the world, after escaping the farm, Desmond goes incognito for a while, showing his skills at avoiding detection, he is eventually caught by a motorcycle license. Desmond however occasionally makes jokes to both friends and enemies. After escaping abstergo, Desmond became more relaxed around friends and became more humorous and flirtatious, however after discovering the bleeding effect, he became worried for his sanity.