[5][page needed] After having been lay abbot of Santa Maria in Sylvis since 1441, in 1445 he succeeded Giuliano Cesarini as archpriest of the Vatican Basilica.

Barbo was elected to succeed Pope Pius II by the accessus in the first ballot of the papal conclave of 30 August 1464[6] with a majority of fourteen of the nineteen cardinals present.

[9] He had a papal tiara made for his own use studded with "diamonds, sapphires, emeralds, topaz, large pearls, and every kind of precious gem".

Five were candidates pressed by kings, placating respectively James II of Cyprus, Edward IV of England, Louis XI of France, Matthias Corvinus of Hungary and Ferdinand I of Naples; one was the able administrator of the Franciscans; and the last two elevated his old tutor and a first cardinal-nephew.

Tensions came to the fore when in attempting to eliminate redundant offices, Paul II proceeded to annul the college of Abbreviators, whose function it was to formulate papal documents; a storm of indignation arose, inasmuch as rhetoricians and poets with humanist training, had long been accustomed to benefiting from employment in such positions.

In February 1468, when Rome was rife with political intrigue fomented by the Roman barons and the neighboring princes, Paul II arrested Platina and other members of the academy on charges of irreligion, immorality, and an alleged conspiracy to assassinate the Pope.

Among other things, Platina reported that Pius II suggested Barbo should have been called Maria Pietissima, as "when he could not obtain what he aimed at by praying, entreating, and requesting, he would join tears to his petitions to make them the sooner believed.

More tangibly, after the crackdown of Paul II, the Roman Academy took on a more religious flavour, turning in part to theology as a means of legitimizing its pursuits.

Just when the King's goodwill disposed the Pope in favor of reconciliation, Paul died suddenly of a heart attack on 26 July 1471.

Although Paul II was a committed opponent of humanist learning, he oversaw and approved the introduction of printing into the Papal States, first at Subiaco in 1464 by Arnold Pannartz and Konrad Sweynheim, and at Rome itself in 1467.

The output of printing presses at this period was, as a matter of course, subject to governmental scrutiny; during Paul II's reign, books produced in the Papal States were largely limited to Latin classical literature and ecclesiastical texts.

But it is certain that although Paul II opposed the humanists, he yet provided for popular amusements: in 1466 he permitted the horse-race that was a feature of Carnival to be run along the main street, the Via Lata, which became known from this annual event as the Via del Corso.

So that nobody felt left out of the event, the Pope instituted races for boys, adult men, old people and Jews, with appropriate prizes for each group.

[24][page needed] William Francis Barry considers that his character was "misunderstood by the Italian courts which never dreamt that a Pope could be an honourable man".