He first appears as a Roman deacon and was frequently employed by his brother, Pope Stephen II, in negotiations with the Lombard kings.
After Stephen's death (April 26, 757) Paul was chosen his successor by those who wished a continuation of the late pope's policy. The new pope's reign was dominated by his relations to the Frankish and Lombard kings and to the Eastern emperor. He adopted an independent tone in informing the exarch in Ravenna of his election, but wrote to Pepin that the Frankish alliance should be maintained unimpaired, being forced to this course by the attitude of the Lombard king, Desiderius. The latter held the cities of Imola, Osimo, Bologna, and Ancona, which were claimed by Rome, and in 758 seized upon the duchies of Spoleto and Benevento.
The same year he visited Rome and compelled Paul to write to Pepin asking him to concede all the Lombard claims except that to Imola; another letter of exactly opposite tenor was sent by the same messenger. Pepin found it advisable to maintain good relations with Desiderius, and Paul accomplished nothing by his double-dealing. Later, however, Pepin gave the pope some support and acted as arbiter between the Roman and Lombard claims.
In 765 the papal privileges were restored in Beneventine and Tuscan territory and partially in Spoleto. Meanwhile, the alienation from Byzantium grew greater. Several times, especially in 759, Paul feared that the Greek emperor would send an armament against Rome; and he lived in continual dread lest Byzantine machinations turn the Frankish influence in favor of the Lombards. This was actually attempted, but Pepin held to his original Italian policy.