It wasn't until the Roman Catholic Relief Act 1829, that the possibility of building a Roman Catholic cathedral in Derry could be contemplated. Fundraising for the building of the cathedral took place from 1840. Work began on the construction of the cathedral in 1849. The cathedral's location is next to Francis Street and Creggan Street in Derry. The total cost of building the cathedral amounted to just over £40,000.

Money was raised not just in Derry and Ireland, but also in America where around £4,000 was raised. The architect commissioned to design the cathedral was James Joseph McCarthy who had already built numerous cathedrals across Ireland. The plan of the cathedral is a simple neo-Gothic expression.[2][3]

The cathedral was officially opened on 4 May 1873 by the then Bishop of Derry, Francis Kelly. The project to build the cathedral's bell tower and spire was postponed, as no funds were available for the project. At first the cathedral's windows were made of plain glass due to lack of funds. It was not until the late 1890s when stained glass windows were installed. Work on the bell tower and spire began on 13 August 1900, with the building contract awarded to Courtney and Co from Belfast. Work was completed on 19 June 1903