Corpus Christi College was founded at a time when universities were putting considerable effort into providing better facilities for the study of Greek and Hebrew. Bishop Richard Fox, the founder of Corpus Christi, and John Claymond, the college's first President, therefore ensured that the library should be adequately stocked with Greek printed books and manuscripts. In a famous letter to Claimond in June 1519, Erasmus predicted a great future for the College and alluded to its well-stocked library.

Claymond gave the library more than half the present collection of Greek manuscripts, besides seven in Hebrew. His Greek books came largely from the collection of William Grocyn, who had gone to Florence in 1488 to study with Angelo Poliziano and Demetrius Chalcondyles, and doubtless acquired some of his manuscripts there. Remarkably, at the end of the fifteenth century there was a local source of supply for some Greek texts, in the person of Ioannes Serbopoulos, a refugee from Constantinople who had taken up residence near Reading, who supplied Grocyn with MSS 23 and 106 in 1499 and 1495 respectively. It is worth noting in passing that when Grocyn arrived in Florence the printing of Greek texts had barely begun, but by the time the College was founded the demand for manuscript copies of the principal texts used by students and scholars was much reduced, thanks largely to the editions issued by Aldus Manutius

After the substantial initial acquisitions of manuscripts the College was not fortunate enough to attract significant additions to its collection, and there is no sign that it contemplated an active policy of enlarging this element of the library's holdings. But it is worth noting that the one manuscript in the collection which is of truly outstanding importance, the ninth-century copy of Aristotle's zoological works (MS 108), was given by one of the Fellows in 1623.