The effect of the early academic and religious changes of the century can be seen in the physical appearance of the town: a great new College, Trinity, was founded by Henry VIII from the two small houses of King's Hall and Michaelhouse; Dr Caius enlarged Gonville Hall to make it almost a new foundation, called Gonville and Caius College, which occupied a large site close to the Old Schools; Emmanuel absorbed the Dominican site, Sidney Sussex that of the Franciscans, and Magdalene absorbed the former Benedictine house of studies known as Buckingham College. These new foundations were concerned with the education of men for the priesthood in the national church, but they, and Trinity especially, attracted for the first time large numbers of lay students.

The size of the official University greatly increased, but the total population of young men in the town included those who came to Cambridge, not so much with the intention of eventual graduation, but to profit from unofficial contacts and extra-curricular activities, and who then went on for a year or so to an Inn of Court in London. These lay students, their servants, and the tailors, fencing-masters, tennis-court-keepers, riding-masters and the like, who came to profit from them, put very great pressure on living accommodation and food-supplies in the town and created serious problems of public order. This was a period when town-gown relationships were very severely strained.

The changing character of the student body is reflected in the curriculum. Henry VIII had issued a series of injunctions to the University in 1536 suppressing the Faculty of Canon Law and forbidding the study of scholastic philosophy. The study of canon law declined, and the Greek and Latin classics, mathematics and Biblical studies now came to the fore.

The changes in the University were perpetuated by successive Royal interventions; the monarchs were concerned with the universities as producers of the future leaders of the reformed church, and the Statutes of 1570 ensured this. They concentrated authority not, as previously, in the Regent Masters and the Proctors, but in the Vice-Chancellor and the Heads.

The endowment by Henry VIII of five professorships, the Regius professorships of divinity, Hebrew, Greek, physic and civil law, emphasised changes in teaching methods and set an example for private donors. The national upheavals of 1640 to 1660, and to a lesser degree of 1688-89, led to disturbances in appointments and discipline, but Royal influence in the shape of Privy Council orders, and of requests for degrees for the court's nominees (mandate degrees) continued until the early eighteenth century.