When the Exarchate of Ravenna finally fell to the Lombards in 751, the Duchy of Rome was completely cut off from the Byzantine Empire, of which it was theoretically still a part. The popes renewed earlier attempts to secure the support of the Franks. In 751, Pope Zachary had Pepin the Short crowned king in place of the powerless Merovingian figurehead king Childeric III. Zachary's successor, Pope Stephen II, later granted Pepin the title Patrician of the Romans. Pepin led a Frankish army into Italy in 754 and 756. Pepin defeated the Lombards – taking control of northern Italy. In 781, Charlemagne codified the regions over which the pope would be temporal sovereign: the Duchy of Rome was key, but the territory was expanded to include Ravenna, the Duchy of the Pentapolis, parts of the Duchy of Benevento, Tuscany, Corsica, Lombardy, and a number of Italian cities. The cooperation between the papacy and the Carolingian dynasty climaxed in 800 when Pope Leo III crowned Charlemagne as 'Emperor of the Romans'.

After the death of Charlemagne (814), the new empire soon disintegrated under his weak successors. There was a power vacuum in Italy as a result of this. This coincided with the rise of Islam in the Arabian Peninsula, North Africa and the Middle East. In the South, there were attacks from the Umayyad Caliphate and the Abbasid Caliphate. The turn of the millennium brought about a period of renewed autonomy in Italian history. In the 11th century, trade slowly recovered as the cities started to grow again. The Papacy regained its authority and undertook a long struggle against the Holy Roman Empire.