In 1841, the Catholic faith was formally brought to Scranton by James Sullivan, a missionary priest who celebrated the first Mass in a house on Shanty Hill, located in what is now the South Side of the city. Within the next seven years the first Catholic church had been built in that section and dedicated by Bishop John Kenrick of Baltimore. In 1853, Rev. James Cullen selected a site for a second Catholic church in Scranton at the corner of Franklin Avenue & Spruce Street. This was to be known as St. Vincent de Paul Church. Before its completion, Father Cullen was replaced by Rev. Moses Whitty, the first pastor of what was to eventually become known as St. Peter's Cathedral.

With the rapidly growing number of newly arrived immigrants, it was soon necessary for Father Whitty to search for a site to construct a new church. Three lots in the 300 block of Wyoming Avenue were purchased for the sum of approximately $ 2,000, a large sum for its day, at the present site of the Cathedral. In 1865 ground was broken at the corner of Linden Street and Wyoming Avenue for the new church. Some deemed it to be "in the woods" as it was far removed from the primary commercial area of the community then located in the Bellevue and Hyde Park areas of the city.On March 10, 1867, Bishop James Wood of Philadelphia blessed the new church. The establishment of the new Diocese of Scranton and the installation of its first Bishop followed quickly in 1868 with the consecration of the Most Rev. William O'Hara. A native of Ireland and the former pastor of Saint Patrick's Church in Philadelphia, Bishop O'Hara was to remain as the" first head of the new diocese until his death three decades later on February 3, 1899.

Beginning in 1883, a project was undertaken to remodel and embellish the church which was now the central church of the diocese. On September 28, 1884 upon completion of the project and satisfaction of all debt incurred, the new Mother Church of the diocese was consecrated by Archbishop P.J. Ryan of Philadelphia, and its name was changed to the Cathedral of St. Peter marking it's new role in the still young diocese comprised of eight counties in northeastern Pennsylvania.