In 1464 St. Mary's was made a Collegiate Church, with the foundation of 'Our Lady's College of Yoghill' by Thomas, 8th Earl of Desmond. It was served by a Warden and Clerks consisting of eight Fellowes and eight choristers.

During the wars of the late 16th Century the church was occupied by the insurgent forces of Gerald, Earl of Desmond, who among other acts of desecration, unroofed the beautiful 15th Century Chancel.

Sir. Walter Raleigh was Mayor of Youghal in 1588 and lived in the Warden's Residence (now known as Myrtle Grove). In 1649, during the Commonwealth, Oliver Cromwell conducted his campaign from Youghal, and delivered a funeral oration from the top of the chest which is still preserved in the church.

George Berkely, Bishop of Cloyne and great philosopher, took up residency as Warden of the College in 1734 and conducted services in the church. John Wesley, also visited Youghal in 1765 and attended Divine Service in St. Marys.

Large-scale works of restoration, including the re-edification of the Chancel, were carried out between 1851 and 1854. A restoration of a remedial nature was carried out between 1970 and 1973. In the late 1980s the Lady Chapel was restored and, in recent years St. Mary's Collegiate Church was given the status of a National Monument of Ireland. In 2005 work began on the restoration of the ancient foundation of the Clerks Choral.