Born in the Episcopal principality of Utrecht of the Holy Roman Empire of the German Nation, Adrian studied at the University of Leuven in the Low Countries, where he rose to the position of professor of theology, also serving as its rector (the equivalent of president or vice-chancellor).

Adrian came to the papacy in the midst of one of its greatest crises, threatened not only by Lutheranism to the north but also by the advance of the Ottoman Turks to the east.

[6] In June 1476, he started his studies at the University of Leuven,[7] where he pursued philosophy, theology and Canon Law, thanks to a scholarship granted by Margaret of York, Duchess of Burgundy.

[4] Ferdinand of Aragon,[10] and subsequently Charles V, appointed Adrian Bishop of Tortosa, which was approved by Pope Leo X on 18 August 1516.

After the death of Jimenez, Adrian was appointed (14 March 1518) General of the Reunited Inquisitions of Castile and Aragon, in which capacity he acted until his departure for Rome.

Charles V was delighted upon hearing that his tutor had been elected to the papacy but soon realised that Adrian VI was determined to reign impartially.

Francis I of France, who feared that Adrian would become a tool of the Emperor, and had uttered threats of a schism, later relented and sent an embassy to present his homage.

[14] Fears of a Spanish Avignon based on the strength of his relationship with the Emperor as his former tutor and regent proved baseless, and Adrian, having notified the College of Cardinals of his acceptance,[15] left for Italy after six months of preparations and trying to decide which route to take, making his solemn entry into Rome on 29 August.

The 1908 edition of the Catholic Encyclopedia characterised the task that faced him: His plan was to attack notorious abuses one by one; however, in his attempt to improve the system of indulgences he was hampered by his cardinals.

He found reduction of the number of matrimonial dispensations to be impossible, as the income had been farmed out for years in advance by Pope Leo X.

At the Diet of Nuremberg, which opened in December 1522, he was represented by Francesco Chieregati, whose private instructions contain the frank admission that the disorder of the Church was perhaps the fault of the Roman Curia itself, and that it should be reformed.

[18][19] However, the former professor and Inquisitor General was strongly opposed to any change in doctrine and demanded that Martin Luther be punished for teaching heresy.

[24] The first series of engravings used to educate Dutch school children at the turn of the 18th century includes Adrian VI in its woodcut on 'Famous Dutch Men and Women' with the following poem: Pope Adrian VI appears as a character in Christopher Marlowe's stage drama The Tragical History of Doctor Faustus (1604).