A church has been located on the site of current St Tewdric's Church since the 6th century. Following the Norman conquest of Wales, the Celtic foundation was rebuilt in the twelfth and thirteenth centuries, in the Early English style. The chancel and nave arcades of the existing church date from those periods, though the west pier of the north arcade dates from the previous century. It was later grandiosely enlarged by John Marshall, the Bishop of Llandaff between 1478 and 1496. Under his stewardship, the aisles were widened, a porch added on the south side, and the tower, built of ashlar blocks, was constructed.
According to the Liber Landavensis, when King Tewdrig fell in battle against the Anglo-Saxons at the River Wye, it was his desire to be buried on Ynys Echni; however the soldiers were unable to get his body there. Instead, he was buried at Mathern by his son Meurig ap Tewdrig. An oratory was built on top of his grave, and the land surrounding it was given to the Celtic Christian Bishops of Llandaff. Nearby Mathern Palace was later built for the use of the bishops.
A stone coffin, thought to contain the remains of Tewdrig, was first discovered when Francis Godwin was bishop in 1614; at that time it was moved to the chancel. An urn containing the heart of another bishop, Miles Salley, was unearthed and reburied at the same time.
In the 1880s, the Church of England ordered a renovation of the church. During the renovation, the stone coffin was rediscovered under the altar, with a skeleton with the skull split by an axe blow, in the same way that Tewdrig supposedly died. However historian Fred Hando claims from an eye-witness account that the skull only had a hole from a spear in it rather than an axe split. The remains were reinterred afterwards. On the wall of the chancel is a late 18th-century inscription noting that Tewdrig is interred in the church, with an addendum noting the rediscovery of the coffin in 1881.
Following restorations, the church now has no visible elements of the original Celtic church. The oldest parts of the church are the arcades of the nave and the arch over the chancel.
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