During the early 16th century, as the Templars were being driven from Italy by the Assassins, the Byzantine Templars arose in the Ottoman Empire, appealing to members of the Greek population and other Christians who longed to see the Byzantine Empire restored and the Ottoman Empire destroyed. Led by the de jure Byzantine Emperor, Manuel Palaiologos, the Byzantine Templars set up their primary headquarters at Derinkuyu in Cappadocia, which had for centuries served as a haven for Greeks against Turkish encroachment. The Byzantine Templars' ultimate aim was to uproot the Ottoman Empire, retake control of Constantinople in particular, and ultimately bring the East and West back under a single rule. For a time, however, they remained relatively quiet.
By 1509, the Templars were aware of the five seals of Altaïr Ibn-La'Ahad. In this year, after an earthquake shook Constantinople, the Templars discovered one of the seals under Topkapı Palace, as the entrance to the seal's chamber had been opened by the seismic activity.
Following this discovery, the Byzantine Templars became more active and militant in their desire to retake Constantinople and find the remaining four seals. The Masyaf expedition and Topkapı seal were entrusted to Manuel Palaiologos, who by then had been supplanted as Templar leader by the younger and more charismatic Ottoman prince Ahmet.
By the beginning of 1511, a Byzantine Templar captain named Leandros had occupied the region surrounding Masyaf, where the library of Altaïr Ibn-La'Ahad was located, though by May 1511, the region had been cleansed of Templars by the Mentor of the Italian Assassins, Ezio Auditore da Firenze, who was visiting Masyaf to learn more of the Assassin Order.
As the Templars plotted to overthrow the Ottomans, many Byzantine soldiers were present in Constantinople by mid-1511. These soldiers rivaled the Constantinople Assassins Guild, and by the month of May, they had seized all of the Assassin Dens for themselves aside from two, with them being one in Galata, and one in the Imperial District, near the Grand Bazaar.
Shortly after Ezio's arrival in the city, the Templars launched an attack on both of the remaining dens, and though they were routed at Galata, they managed to take the den at the Grand Bazaar. However, this would prove to be a temporary victory, as the Assassins retook the den shortly after. Over the 11 months that Ezio spent in the city, he managed to retake the dens one by one and severely weaken the Templars, until March 1512.
Following this, Ezio left for Cappadocia in search of Palaiologos, who possessed the last seal. Ultimately, Ezio killed Manuel and claimed the seal for himself, though, as he was about to leave, Ahmet arrived on a ship with Byzantines, revealing that he was the true mastermind behind the Masyaf expedition, and that he would take Ezio's friend, Sofia Sartor, hostage.
Unable to reach him, Ezio was forced to pursue Ahmet back to Constantinople, where he discovered Ahmet had indeed taken Sofia hostage in her bookstore, in the process killing the leader of the Assassins Guild, Yusuf Tazim, to whose back he pinned a taunting note addressed to Ezio, with a dagger. Ezio rallied the Assassins Guild for a retaliatory attack on the Harbor of Theodosius, where Ezio once again confronted Ahmet, who threatened to kill Sofia unless the seals were all handed over at the Galata Tower.
After a tense handover on the battlements of the old Genovese walls adjoining the Tower, Ahmet pointed out what appeared to be Sofia with a burlap sack over her head being held by a Byzantine soldier at the top of the Tower. Upon rescuing her, Ezio realised she was a decoy and Sofia was actually being hanged in a remote square, seemingly too far to reach, but using a parachute, Ezio was able to glide over and save Sofia from suffocating. Promising her answers later, they both hijacked a nearby carriage and took off into the countryside after Ahmet, who was on his way to Masyaf to open the vault. After a prolonged chase through the countryside, Ezio and Ahmet were discovered by Ahmet's brother Selim and his Janissaries. After informing Ahmet of their father, Bayezid II's decision to abdicate to him, Selim threw Ahmet to his death over a cliff edge, thus destroying the Byzantine Templar Order.
During the early 16th century, the Templars set up their headquarters in Cappadocia, after being driven from their previous base in Rome by the Assassins. There, the Templars set up prisons and instated themselves as the rulers of the city, filling the streets with Byzantine soldiers.
Palaiologos resided in Cappadocia for some time after his family lost their hold on the Byzantine throne. He, along with his bodyguard and fellow Templar, Shahkulu, governed much of the city and held power within its walls until Ezio's arrival.
- The frequently spoken name "Byzantine" is an anachronism, as this name was given to the Eastern Roman Empire by later historians, in order to distinguish between it and ancient Rome. As such, the Byzantines would have referred to themselves as "Romans", "Greeks" and/or "Hellenes" (Romaioi, Graikoi and Ellines in Greek respectively) since they were the political continuation of the Roman Empire in the east, as well as the direct heirs and guardians of Hellenic civilization. Despite the word Byzantine first being used roughly thirty years after the events of Assassin's Creed: Revelations, and widespread use of the word not occurring until the 19th century, Manuel Palaiologos and many other characters still use the term, likely for the sake of audience recognition.
- Once Ezio had liberated all of the Templar Dens and completed the Master Assassin memories, Byzantine soldiers would rarely be encountered in Constantinople, aside from a few lingering patrols in the Constantine District, the bodyguards of Templar officials once notoriety was high enough, and patrols of Byzantines that would occasionally appear and ambush him (usually consisting of two or three militia and a Varangian).