Pope John VI, who succeeded Pope Sergius I as the eighty-fifth head of the Church, was born in Ephesus, Greece. He later came to Rome and continued his priestly ministry there. He was installed on the throne of St. Peter during a period of political instability.

Pope John VI was elected as the new pope on October 30, AD 701, about seven weeks after the death of Pope Sergius I. His consecration took place on the same day. The reason for this was that the consecration of the Bishop of Rome could be carried out without waiting for the approval of the Roman Emperor.

When the lord of Benevento attempted to seize Church property, Pope John resisted such attempts. He also offered a large ransom for the release of those who had been imprisoned in an effort to protect the Church and the papal borders. The opportune intervention of the pope saved the life of Theophylact, the emperor's exarch when he was attacked by mutineers in the Italian army.

In AD 703, Wilfrid, Bishop of York, having been expelled from his see for the third time, sought refuge with the pope in Rome. Pope John sent a delegation to discuss the matter in Rome. In AD 704, a four-month-long synod was convened, and Bishop Wilfrid declared his support for the bishop.

The only surviving document of Pope John VI is a letter he wrote to the kings of Northumbria and Mercia after the synod. In this letter, the pope asked the kings of Northumbria and Mercia to request the Archbishop of Canterbury to find a solution to the issue of the Bishop of York through a synod. However, if such an attempt failed, the pope also stipulated that all parties should come to Rome to try to resolve the issue.

Pope John VI died on January 11, AD 705. His body is buried in St. Peter's Basilica.