In addition to being a parish church in the Diocese of Ely, it is the University Church for the University of Cambridge. As such it has a minor role in the University's legislation: for example, University Officers must live within 20 miles of Great St Mary's, and undergraduates within three. The church also hosts University Sermons, and houses the University Organ and the University Clock. The latter chimes the Cambridge Chimes which were later used by the clock tower of the Houses of Parliament ("Big Ben").
Many notable sermons have been preached from Great St Mary’s pulpit down the centuries. Many of the great names from the Reformation have addressed the Great St Mary’s congregation including Latimer, Ridley, Bray, etc. The Reformation theologian Martin Bucer was buried in the church, but his body was dug up and burnt during the reign of Queen Mary. However a memorial plaque marks the place of his tomb.
St Mary the Great is unusual in housing two self-contained pipe organs, one for the 'regular' congregation, and the other the 'University Organ'. The latter was originally purchased in 1698, but heavily rebuilt until the current version was completed in 1870. The organ was extensively restored in 1995 resulting in its rededication in January 1996.