In its earliest days, the University had no premises of its own: it relied on parish churches, especially Great St Mary's and St Benedict's (or 'Bene't's') and on the premises of the religious orders, as sites for its public ceremonies. Lectures, disputations and lodgings were found in private houses which frequently changed hands or went out of use. Soon a few groups of Regent Masters, lawyers and theologians, began to build or hire larger premises for teaching and lodging. A few of the hostels survived until the sixteenth century when they were often acquired as part of the premises of Colleges. Unlike the Colleges, hostels had few endowments and were always privately owned.

Meanwhile during the late fourteenth century and after, the University began to acquire property on the site today known as Senate-House Hill, and to build on it a group of buildings called the 'Schools' - some of which survive today as the 'Old' Schools. Here were the teaching rooms of the higher faculties - the first building to be erected was the Divinity School - where lectures and disputations were held, the chapel, the library, and the treasury, with its chests and muniments. Most of the land and buildings in the town was still in private hands, or in those of religious houses, although from the late thirteenth century much was already passing to the new institutions called Colleges. Pious donors provided these Colleges in the first place for a small number of advanced students in law or divinity who would pray for the souls of their benefactors. It was later that the Colleges housed the very young undergraduates who had previously been lodged in hostels or private houses.

The earliest College was St Peter's or 'Peterhouse', founded in 1284 by Hugh Balsham, Bishop of Ely. King's Hall, 1317, was intended by its founder, Edward II, to provide recruits to the higher civil service. Michaelhouse, Clare, Pembroke, Gonville Hall, Trinity Hall, Corpus Christi, King's, Queens' and St Catharine's followed during the next 100 years. Three late foundations, Jesus, Christ's and St John's, emerged from the dissolution of small religious houses before 1520 and, like the King's Hall, provided for younger scholars as well as 'post-graduates'.

Before the middle of the sixteenth century, the Colleges began to play a decisive part in University life. They now nominated the Proctors from among their own members for the annual term of office, and their heads often served with the Vice-Chancellor and senior doctors as members of an advisory council which was soon to be called the Caput Senatus. From the sixteenth century until almost the end of the twentieth, the Head of one of the Colleges always held the office of Vice-Chancellor.

One of the key figures in Cambridge at this time was John Fisher, who was successively Master of Michaelhouse, Proctor, Vice-Chancellor, Chancellor (1509-35) and President of Queens'. As adviser to King Henry VII's mother, Lady Margaret Beaufort, he was instrumental in the foundation of Christ's and St John's; equally importantly he evidently inspired the establishment of the first endowed university teaching post, the Lady Margaret Professorship of Divinity. He also attracted to Cambridge a number of scholars - notably Erasmus of Rotterdam - who encouraged the 'new learning' in Greek and Hebrew, helping to clear the way for the half-theological, half-philosophical speculations which produced the reformation of the church and the dissolution of the monasteries.