The Welsh diocese of the former Kingdom of Gwynedd was founded c. 546 by Saint Deiniol as the first Bishop of Gwynedd in the Diocese of Bangor. Around 615 AD the current location of St. Cadwaladr's Church was established as royal monastery by the Kings of Gwynedd.

King Cadfan ap Iago had been buried in the church. Cadfan's grandson Cadwaladr ap Cadwallon (Cadwaladr the blessed) was the patron Saint of the church which is named after him. King Cadwaladr retired to Llangadwaladr to become a monk, he died in Rome in 664 and his body was brought back and buried here.

The church was rebuilt in the 12th and 13th centuries with the addition of the nave. The chancel was added in the 14th century. Unusually, the advowson of the benefice lay with the monarch rather than the bishop, until Disestablishment (1920).