A Roman abbot of noble birth, Mellitus was sent by Pope Gregory the Great to England at the head of a group of missionaries in A.D. 601, to reinforce the work of Augustine of Canterbury. After his departure, Gregory sent him a famous letter which modified his previous ruling to Augustine concerning pagan places of worship. Gregory now told Mellitus to tell Augustine not to destroy the temples of the Saxons but only their idols. The pagan places of worship should be converted into churches and their feasts taken over and directed to Christian purposes.

In A.D. 604, Augustine consecrated Mellitus missionary bishop of the East Saxons, with his seat at London, where Ethelbert (king of Kent and overlord of southern England) caused the first Church of St Paul to be built for the new bishop.
As bishop of London, Mellitus travelled to Rome to consult with Pope Boniface IV about the Church in England, taking part while there in a synod of Italian bishops concerning the monastic life and their relations with bishops.

Several years into his episcopate, evangelisation of the East Saxons was arrested when Sæberht, the Christian king of the East Saxons, died, and his three pagan sons succeeded him and expelled Mellitus. The occasion for this was said to be Mellitus’ refusal to give holy communion to the unbaptised princes. With this reversal in Essex came a corresponding and greater setback to missionary work in Kent on the death of king Ethelbert, Mellitus and another bishop, Justus, retired to Gaul.

On the conversion of the new king, they were recalled to England by Laurence, Archbishop of Canterbury. Lacking the support of a strong Christian ruler, Mellitus was unable to return to London and the East Saxons.
In A.D. 619, he succeeded Laurence as Archbishop of Canterbury and carried out his ministry ably despite chronic debility from gout. Mellitus died in A.D. 624 and was buried near Augustine, in the abbey Church of Saints Peter and Paul in Canterbury.