Initially invaded by the Celts by A.D. 500 the main insurgents were Angles, a Germanic tribe from Jutland, who were skilled in the use of shallow vessels and used the East Anglian rivers as routes into Britain. The Nene, Ouse and Cam valleys were understandably the first colonised and by A.D. 500 the colonisation spread out of Cambridgeshire, Cambridge being quickly colonised. The Cam tributaries experienced the early settlements at Linton, Haslingfield and from Newmarket to Balsham. The Angles took over British sites giving them English names. Only a half-dozen Celtic place names remain in the county such as Girton, Comberton and Chatteris. Neglect of the Roman engineering works and land subsidence after A.D. 450 reduced drained fenland to Marsh, isolating Ely and other islands. Within these areas lived a dark-haired, independent people, called the Gywre, possibly Celtic in origin.

During the 7th century upland Cambridgeshire was disputed by three tribes, the west belonged to Middle Anglia, the far south to the East Saxons and the rest to East Anglia. This led to warfare between the tribes, initially the East Anglians were the powerful tribe forcing Middle Anglia back along the chalk belt but then Middle Anglia was seiazed by the powerful Middle kingdom, Mercia, under king Penda who then attacked East Anglia, defeating Siegbert and Anna the rules in A.D. 653-4.

This conflict may have been the reason for the building of four massive dykes at Heydon, Pampisford, Balsham and Reach. One of these, Devil's Dyke, is where king Anna established his court, at Exning. The dykes did not prevent the Mercians conquering East Anglia which was complete by A.D. 700.

During this period several abbeys were built on the fens, Crowlnd, Thorney and Peterborough being three. The greatest was founded by East Anglia, namely Ely. Sigbert established the first bishopric under Felix, showing favour to the Celtic mystic Fursa. Anan's daughter, Ethelreda, influenced by Felix pledged her virginity to Christ but made two political marraiges, the first to Tonbert of the Gyrwe, bringing Ely as her inheritance and then to the Northumbrian pronce Ecgfrith. In 672 Ethelreda fled from the latter when he demanded consummation of the marriage. She sought sanctuary on the Isle of Ely establishing a double abbey of monks and nuns under her abbess.