The arrival of the Vikings in Cambridge was recorded in the Anglo-Saxon Chronicle in 875. Viking rule, the Danelaw, had been imposed by 878. The Vikings' vigorous trading habits caused Cambridge to grow rapidly. During this period the centre of the town shifted from Castle Hill on the left bank of the river to the area now known as the Quayside on the right bank. After the Viking period, the Saxons enjoyed a return to power, building churches such as St Bene't's Church, wharves, merchant houses and a mint, which produced coins with the town's name abbreviated to "Grant".

Cambridge played a significant role in the early part of the English Civil War as it was the headquarters of the Eastern Counties Association, an organisation administering a regional East Anglian army, which became the mainstay of the Parliamentarian military effort prior to the formation of the New Model Army. In 1643 control of the town was given by Parliament to Oliver Cromwell, who had been educated at the University's Sidney Sussex College. The town's castle was fortified, with troops garrisoned there and some bridges destroyed to aid the defence. Although Royalist forces came within 2 miles (3 km) of the town in 1644, the defences were never used and the garrison was stood down the following year.

During the Second World War, Cambridge was an important centre for defence of the east coast. The town became a military centre, with an R.A.F. training centre and the regional headquarters for Norfolk, Suffolk, Essex, Cambridgeshire, Huntingdonshire, Hertfordshire, and Bedfordshire established during the conflict. The town itself escaped relatively lightly from German bombing raids, which were mainly targeted at the railway. 29 people were killed and no historic buildings were damaged. In 1944, a secret meeting of military leaders held in Trinity College laid the foundation for the allied invasion of Europe. During the war Cambridge served as an evacuation centre for over 7,000 people from London, as well as for parts of the University of London.

Cambridge was granted its city charter in 1951 in recognition of its history, administrative importance and economic success.

The city gained its second University in 1992 when Anglia Polytechnic became Anglia Polytechnic University. Renamed Anglia Ruskin University in 2005, the institution has its origins in the Cambridge School of Art opened in 1858 by John Ruskin. The Open University also has a presence in the city, with an office operating on Hills Road.