By Revelations, despite his earlier conflict with the Assassins, Piri joined the Ottoman Assassin Brotherhood in 1506 to serve as a scholar and technician, and even eventually progressed to the rank of Master Assassin. Later, he acts as a pyrotechnician, scholar and cartographer for the Ottoman Assassin Brotherhood. He meets Ezio later in the game, and they start discussing bombs.

Apart from the maps, the book also contained detailed information on the major ports, bays, gulfs, capes, peninsulas, islands, straits and ideal shelters of the Mediterranean Sea, as well as techniques of navigation and navigation-related information on astronomy, together with information about the local people of each country and city and the curious aspects of their culture. There are thirty legends around the world map, twenty-nine in Turkish and one in Arabic; the latter gives the date as the month Muharrem of AH 919 AH (i.e. the spring of 1513) but most studies have identified the more probable date of completion as 1521.

The second section is entirely composed of portolan charts and cruise guides. Each topic contains the map of an island or coastline. In the first book (1521), this section has a total of 132 portolan charts, while the second book (1525) has a total of 210 portolan charts. The second section starts with the description of the Dardanelles Strait and continues with the islands and coastlines of the Aegean Sea, Ionian Sea, Adriatic Sea, Tyrrhenian Sea, Ligurian Sea, the French Riviera, the Balearic Islands, the coasts of Spain, the Strait of Gibraltar, the Canary Islands, the coasts of North Africa, Egypt and the River Nile, the Levant and the coastline of Anatolia. This section also includes descriptions and drawings of the famous monuments and buildings in every city, as well as biographic information about Piri Reis who also explains the reasons why he preferred to collect these charts in a book instead of drawing a single map, which would not be able to contain so much information and detail.

By 1516, he was again at sea as a ship captain in the Ottoman fleet. He took part in the 1516–17 Ottoman conquest of Egypt. In 1522 he participated in the Siege of Rhodes against the Knights of St. John, which ended with the island's surrender to the Ottomans on 25 December 1522 and the permanent departure of the Knights from Rhodes on 1 January 1523 (the Knights relocated briefly to Sicily and later permanently to Malta). In 1524 he captained the ship that took the Ottoman Grand Vizier Pargalı İbrahim Pasha to Egypt.

In 1528, Piri Reis drew a second world map, of which a small fragment (showing Greenland and North America from Labrador and Newfoundland in the north to Florida, Cuba, Hispaniola, Jamaica and parts of Central America in the south) still survives. According to his imprinting text, he had drawn his maps using about 20 foreign charts and mappae mundi (Arab, Spanish, Portuguese, Chinese, Indian and Greek) including one by Christopher Columbus. He was executed in 1553.

In 1547, Piri had risen to the rank of Reis (admiral) as the Commander of the Ottoman Fleet in the Indian Ocean and Admiral of the Fleet in Egypt, headquartered in Suez. On 26 February 1548 he recaptured Aden from the Portuguese, followed in 1552 by the sack of Muscat, which Portugal had occupied since 1507, and the strategically important island of Kish. Turning further east, Piri Reis attempted to capture the island of Hormuz in the Strait of Hormuz, at the entrance of the Persian Gulf, unsuccessfully. When the Portuguese turned their attention to the Persian Gulf, Piri Reis occupied the Qatar peninsula to deprive the Portuguese of suitable bases on the Arabian coast.

He then returned to Egypt, an old man approaching the age of 90. When he refused to support the Ottoman Vali (Governor) of Basra, Kubad Pasha, in another campaign against the Portuguese in the northern Persian Gulf, Piri Reis was beheaded in 1553.

A century after Piri's death and during the second half of the 17th century, a third version of his book was produced, which left the text of the second version unaffected while enriching the cartographical part of the manuscript. It included additional new large-scale maps, mostly copies of the Italian (from Battista Agnese and Jacopo Gastaldi) and Dutch (Abraham Ortelius) works of the previous century. These maps were much more accurate and depict the Black Sea, which was not included in the original.