They would dedicate all of their time to the Liturgy of the Hours, and mainly opposed the beliefs of the established Roman Catholic Church.

Upon hearing of their dissident behavior, the bishop of the Roman Catholic Archdiocese of Cambrai (to which Antwerp belonged at the time) then sent Norbert of Xanten to discipline them.

The 8 other secular canons prefer to keep their freedom and move to a different location, a chapel dedicated to Our Lady, the Virgin Mary.

The cloverleaf-shaped eastern section with a full aisle had a width of no less than 42 m. In 1294, the church gets a novum opus extension, indicating the first signs of gothic architecture.

During the night of 5–6 October 1533, the new church was largely gutted by fire; however, Lancelot II of Ursel managed to save the building.

The eye-witness Richard Clough, a Welsh Protestant merchant then in Antwerp, wrote that the cathedral: "looked like a hell, with above 10,000 torches burning, and such a noise as if heaven and earth had got together, with falling of images and beating down of costly works, such sort that the spoil was so great that a man could not well pass through the church.

"[7][8] Nicolas Sander, an English Catholic exile who was a professor of theology at Louvain, described the destruction in the church: ... these fresh followers of this new preaching threw down the graven [sculpted] and defaced the painted images, not only of Our Lady but of all others in the town.

They tore the curtains, dashed in pieces the carved work of brass and stone, brake the altars, spoilt the clothes and corporesses, wrested the irons, conveyed away or brake the chalices and vestiments, pulled up the brass of the gravestones, not sparing the glass and seats which were made about the pillars of the church for men to sit in. ...

Sixteenth-century choirmasters included Antoine Barbe, Geert van Turnhout, Séverin Cornet, and Andreas Pevernage.

[10] Organists who worked at the cathedral include Henry Bredemers (1493–1501), who went on to become a teacher to Philip the Handsome's children and the renowned English composer John Bull (1615–1628), who fled to Flanders from his home country escaping justice.

Inside the Cathedral some important graves still can be found, amongst them family members of the noble houses of Rubens, Fourment, Goubau, Tucher, Plantin, Moretus, de Borrekens, etc.