Then in the 14th century a second Cathedral was built to the east of the original Cathedral which used the Santuary and Chancel of the 12th century Cathedral as the entrance. This building served as the Catholics Cathedral in Tuam until the late 16th century when one William Mullaly was appointed the first Protestant Archbishop of Tuam by Queen Elizabeth the first of England. This led to the Catholic clergy being dispossessed and it wasn't until 1783 that the Catholic clergy were allowed to build a small parish Church in the Town.

In 1833 an act of amalgamation was passed in the British parliament which united the Church of Ireland dioceses of Tuam, Killala and Achonry which consists of most of the West of Ireland. This led to the see of Tuam being demoted to the rank of Bishop from 1839.

1861 saw the railways come to Tuam and this led to a sizeable influx of people of the Anglican tradition coming to the area, working on the railways and also as part of the increased garrison presence in the Town. This necessitated the building of the third Cathedral on the site and this Cathedral was completed in 1878. While the Church of Ireland congregation declined following the establishment of the Irish Free State in 1922 this third Cathedral is still used today for the Sunday Service which takes place at 12.00 noon

This third Cathedral contains relics of the Town's past glories, The High Cross which is classed as a National monument was removed to St. Mary's Cathedral in 1992. The 12th century chancel arch in the Hiberno Romanesque style and also the base of another cross which also dates from the late 12th century. Also in this Cathedral one can see some stained glass windows which depict the faces of real people, former parishioners in the Cathedral. The West window of the Cathedral depicts the scene of the transfiguration of our Lord. It is seen at its best when the sun is beginning to set during the summer months, the colours of the window come vividly to life. This window which was the gift of the Bernard Family was installed in the Cathedral in 1913 and is believed to be one of the finest examples of the transfiguration in Western Europe. Underneath this window are seven small windows referred to as lights. The centre window depicts Christ the King and is erected to the memory of Sir Thomas Deane, Architect of the third Cathedral. The other windows depict the prophets of the old testament beginning with Moses, David, Solomon, Ezra, Malachi and John the Baptist.