The earliest specific references to a library of the University at Cambridge are to be found in the wills (both proved in March 1416) of William Hunden and William Loring, the former bequeathing to it three volumes "to remain forever in the new library at Cambridge for the use of graduates and scholars in residence", and the latter all his books of civil law "to remain forever in the common library of all scholars of the University." There are, of course, earlier references to books in the possession of the university. Richard de Lyng, three times Chancellor of the University, who died in 1355, is included as the donor of a chest of books in an early service in commemoration of the university's benefactors; and an inventory made in 1363 of the contents of the university's common chest includes a small number of books as well as money, vestments, charters, etc. Thus, although the earliest surviving collection of the university's statutes, believed to have been compiled about 1250, and the collection of statutes written at the end of the fourteenth century to replace originals destroyed in 1381 make no mention either of a library or of a librarian, the available evidence suggests that from the middle of the fourteenth century at least, the university owned and kept in chests in its treasury a small collection of books which began to be expanded and was formally established as the Common Library of the University during the second decade of the fifteenth century.

This expansion was made possible because at this period the university began to develop the site known as the Old Schools which housed its first regular lecture rooms and other essential offices and institutions, comprising four ranges of two-storied buildings facing the four points of the compass so as to enclose a cental courtyard. The northern range, containing a school of theology below and a chapel above, was completed around the year 1400 and was followed by the ranges on the west (a school of canon law below and a library above, in course of erection in 1420), south (philosophy and civil law below and a library above, 1457–ca. 1470), and east (offices below and a library above, 1470–1475). For the building of the upper story of the eastern range the university was indebted to the generosity of its Chancellor Thomas Rotherham (1423–1500), Archbishop of York. The other buildings were financed, slowly and painfully, by the university itself, the surviving accounts providing ample evidence of its impoverished condition.

It was thus on the upper story of the western range that the University Library found its first home, and it is the library as it was there established that its earliest surviving catalogue (preserved in the University Archives) portrays. This catalogue, entitled A register of the books given by various benefactors to the Common Library of the University of Cambridge, lists 122 volumes in nine subject divisions; sets out the contents of each volume, with their authors, at length; identifies each volume by quoting the first word of its second leaf and the first word of its last leaf but one; and names the donors (thirty-one in all) of ninety-nine of the books. Analysis of this catalogue shows that it is the work of seven successive hands and also shows the library first as it was in 1424 and then as it developed down to about 1440. More than half of its contents were works of theology and religion, and there were twenty-three volumes of canon law. The writers of ancient Rome were represented by Lucan alone, and the early Christian poets and the English chroniclers were entirely absent. Of the recorded donors the most eminent in affairs of church and state were William Loring (a benefactor of Merton College, Oxford, also), Richard Holme (Warden of the King's Hall at Cambridge and councillor to Richard II, Henry IV, and Henry V), John Aylemer (Warden of New College, Oxford, and a friend of William of Wykeham), and Thomas Langley (Bishop of Durham, a cardinal, and twice Chancellor of England). Of the remainder two were successive Masters of Peterhouse (Thomas de Castro Bernardi and John Holbroke) and nine were Fellows of Cambridge colleges. Eleven others were described as magistri and may be presumed to have been Cambridge graduates, though no trace of them can be found in the surviving records of the university and colleges.

By the time the library's second earliest catalogue was drawn up in 1473 the collection had been moved into the room on the upper story of the newly completed south range. This catalogue (also preserved in the University Archives) shows 330 volumes disposed on seventeen lectern cases each of which had hanging at its end a written "table" of the books it contained. Religion and theology still accounted for more than half the collection; but there were some significant newcomers among the authors now represented, including Ovid, the younger Seneca, Cicero, Josephus, and Petrarch. The most "contemporary" authors were William Lyndwode (1375?–1446) and the first Provost of King's College, William Millington; and since Millington (who had been one of the overseers of the building accounts) lived probably until 1466, it may be that we must accord him the distinction of having been the first author ever to see his own works on the library's shelves. This catalogue of 1473 is less informative than its predecessor, but some of the additional books listed in it can be associated with known benefactors. By far the most important of them was Walter Crome, a Fellow of Gonville Hall (later Gonville and Caius College), who died as Rector of St Benet's Sherehog, London, in 1453, bequeathing ninety-three volumes to the university and seven to his college.

The library room that Thomas Rotherham built and furnished with books ran the whole length of the eastern range of the Schools and was entered at its south end by way of a turret stair that also gave access to the other library room in the southern range. These two rooms, which for more than 200 years proved sufficient (and for a time more than sufficient) to hold the university's entire library, provided also a natural division of its contents, the south room holding the "common library" of the university while the east room, to which there was only restricted access, held the "new library" or "library of our Lord Chancellor", as it was first known. Unfortunately no contemporary list of Rotherham's donations survives, though references to gifts of unspecified books received from him are not infrequent in the university's records during the last quarter of the fifteenth century. It is certain, however, that among them were the first printed books which the university ever possessed, and there is reason to conjecture that by 1500, when Rotherham died, the number of volumes in both library rooms together had risen to perhaps 600. They were, however, still primarily medieval in content, for the fresh air of the Renaissance came late to Cambridge, where there was no dominant figure to establish by influence and example a school of modern learning. It was not until 1511 that John Fisher brought Erasmus to Cambridge and not until 1518 that the university established a lectureship in Greek. Although soon afterwards Roger Ascham would write of the enthusiasm with which Greek studies were being pursued at Cambridge, the holdings of the University Library did not reflect that enthusiasm until 1529 when, shortly before his translation to Durham, Cuthbert Tunstal, Bishop of London, gave the university a number of Greek texts, both manuscript and printed, each with a gift inscription in his own fine hand. To these books, which included the editio princeps of Homer and the first volume of the Aldine Aristotle, Tunstal added a copy of the Complutensian Bible [Sel.2.69–74] and a very fine copy, printed on vellum, of the first English arithmetic book, his own De arte supputandi [Sel.3.262].

Of the library's administration during these early years little is known for certain. Its general superintendence lay, as at Oxford, with the University Chaplain, to whom also were entrusted the vestments, plate, and books of religion pertaining to the University Chapel in the northern range of the Schools, the jewelled cross which he carried on processional occasions, and the general security of the Schools themselves. There were, however, no statutes or regulations which defined in detail his duties in the library. The framing of general decisions concerning the use of the library lay with the body of Regent Masters, whose earliest recorded regulation is of 1471–72, when they took the right of admission to the library away from undergraduates, unless accompanied by a graduate, because they had abused its contents, and ruled that nonresident graduates might only enter the library in their proper academical address. In 1500 they permitted the use of the library to members of religious houses who had been sent to study at the university, and several "graces" of the Regents are recorded during the early years of the sixteenth century granting this permission to named individuals. Of the same period also are several graces permitting the borrowing by specified persons of specified books for specified periods, though the earliest recorded grace of this kind (it permitted Rotherham's servant to borrow a book which in all probability Rotherham himself had given) is of 1487.