Corpus was founded in 1517 by Richard Foxe, Bishop of Winchester and a trusted diplomatic and political adviser to King Henry VII. Bishop Foxe had originally intended the College for the training of monks; if he had followed through with this plan, the College would probably have been dissolved in the Reformation of the next generation. Instead, he decided that the College should be a place of Renaissance learning for the education of young men in the humanities and the sciences.

The beautiful main quad, with its tower, dining hall, library and adjoining chapel was planned and completed under Foxe's guidance. Catherine of Aragon was a friend of the College's first President, John Claimond, and often visited him in his College lodgings while her husband, Henry VIII, hunted at nearby Woodstock. Another early visitor was the great humanist scholar, Erasmus, who wrote admiringly of the College's library, while Juan Luis Vives, tutor to Princess (later Queen) Mary was a fellow of the college in its early years.

Members of the College played a central role in the religious disputes of the sixteenth and seventeenth centuries. One of its earliest Fellows, Reginald Pole, was Archbishop of Canterbury under Queen Mary. One of its early graduates was the renowned Protestant scholar Richard Hooker. The College's seventh President, John Rainolds, was a key organizer and translator of the 1611 Authorized Version of the Bible.

In the eighteenth century, the College was able to expand following the construction of a second quad and the fine neoclassical Fellows' Building overlooking Christ Church Meadow. One of its graduates in this period was James Oglethorpe - soldier, prison reformer, member of Parliament, and founder of the colony that later became the American state of Georgia.
In the nineteenth century, Corpus was one of the first colleges to recruit its students in open competition. These included Thomas Arnold, a famous educational reformer and headmaster of Rugby School; John Keble, the Christian poet and leader of the Anglo-Catholic revival in England; C.P. Scott, the most famous newspaper editor of his day; William Hailey, a distinguished colonial administrator; and the Poet Laureate Robert Bridges. The art historian, John Ruskin, was a Fellow. In the twentieth century its graduates have included the philosophers Isaiah Berlin and Thomas Nagel, the writer Vikram Seth and David Miliband, a Cabinet minister in the current Labour government.

For most of its history the College has been famed for its strength in the humanities, especially in Classics, but over the past fifty years or so, the natural and social sciences have come to occupy an equally important place in the make-up of the Fellowship and student body.